MedWorm: Huntington's Disease

Neurodegenerative disorders: A neuroprotective role for sirtuin 1

Nature Reviews Drug Discovery — Wed, 01 Feb 2012 05:00:00 +0100

Nature Reviews Drug Discovery 11, 108 (2012). doi:10.1038/nrd3672 Author: Charlotte Harrison Cellular metabolism has a key role in the pathogenesis of Huntington's disease (HD), which is caused by the accumulation of mutant huntingtin protein (HTT). These two studies show that sirtuin 1 (SIRT1), an NAD-dependent protein deacetylase involved in the control of cellular metabolism, has neuroprotective (Source: Nature Reviews Drug Discovery)

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Evaluation and initial in vitro and ex vivo characterisation of the potential positron emission tomography ligand, BU99008 (2‐(4,5‐Dihydro‐1H‐imidazol‐2‐yl)‐1‐methyl‐1H‐indole), for the Imidazoline2 binding site

Synapse — Tue, 31 Jan 2012 05:00:00 +0100

AbstractThe density of the Imidazoline2 binding site (I2BS) has been shown to change in psychiatric conditions such as depression and addiction, along with neurodegenerative disorders such as Alzheimer's disease and Huntington's chorea. The presence of I2BS on glial cells and the possibility that they may in some way regulate glial fibrillary acidic protein (GFAP), has led to increased interest into the role of I2BS and I2BS ligands in conditions characterised by marked gliosis. In addition, it has been suggested that I2BS may be a marker for human glioblastomas. Therefore the development of a positron emission tomography (PET) radioligand for the I2BS would be of major benefit in our understanding of these conditions. We now report the successful synthesis and initial pharmacological eval...

Substance abuse may be a risk factor for earlier onset of Huntington disease

Journal of Neurology — Tue, 24 Jan 2012 18:09:48 +0100

This study investigated the relationships between alcohol, drug, and tobacco abuse and HD age of onset in 136 participants with symptomatic HD. CAG repeat length was used as a covariate in all analyses, as it represents the most significant determinant of HD age of onset. The relationship between substance abuse, HD age of onset, and sex was also examined, as women may experience greater medical harm from substance abuse. Lifetime alcohol abuse and lifetime drug abuse were associated with earlier age of HD onset; a similar trend was seen for current tobacco abuse. For women, lifetime alcohol abuse was associated with earlier onset of HD, with a similar trend for lifetime drug abuse. However, alcohol, drug, and tobacco abuse were not significantly associated with age of onset in men. ...

Stem Cells Show Promise For Delivering Gene Therapy For Huntington's Disease

Health News from Medical News Today — Tue, 24 Jan 2012 08:00:00 +0100

A team of researchers at the UC Davis Institute for Regenerative Cures has developed a technique for using stem cells to deliver therapy that specifically targets the genetic abnormality found in Huntington's disease, a hereditary brain disorder that causes progressive uncontrolled movements, dementia and death. The findings, now available online in the journal Molecular and Cellular Neuroscience, suggest a promising approach that might block the disease from advancing... (Source: Health News from Medical News Today)

Dietary intake of polyunsaturated fatty acids and risk of hip fracture in men and women

Osteoporosis International — Tue, 24 Jan 2012 07:26:51 +0100

Conclusions This study does not support a significant role for PUFA intake in the prevention of hip fractures, although low total PUFA, n-6 PUFA, or linoleic acid intakes may increase the risk in women. Content Type Journal ArticleCategory Original ArticlePages 1-10DOI 10.1007/s00198-012-1903-3Authors J. K. Virtanen, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, P.O. Box 1627, 70211 Kuopio, FinlandD. Mozaffarian, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USAW. C. Willett, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USAD. Feskanich, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Ha...

Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes.

Acta Pharmacologica Sinica — Mon, 23 Jan 2012 05:00:00 +0100

Conclusion:Rapamcin, an autophagy stimulator, can prevent the suppression of GLT-1 expression and glutamate uptake by mutant Htt-552 in cultured astrocytes. PMID: 22266730 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)

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Huntington's Disease: Advocacy Driving Science.

Annual Review of Medicine — Fri, 20 Jan 2012 09:01:39 +0100

Authors: Wexler NS Abstract My mother, Leonore, was diagnosed with Huntington's disease (HD) in 1968 at age 53. I was 23, my sister Alice 26, and our father, Milton Wexler, 60 years old. The same year, our father created the Hereditary Disease Foundation (HDF), dedicated to finding treatments and cures for HD. HD is an autosomal dominant, neurodegenerative disorder. Alice and I each have a 50% chance of inheriting and dying from the disorder. Over the past 43 years, we have been proud to change the face of science. Through Milton Wexler Interdisciplinary Workshops, judicious funding, and focusing on innovation and creativity, the HDF is an integral partner in key discoveries. The HDF recruited and supported >100 scientists worldwide who worked together as the Huntington's Diseas...

Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease.

Experimental Neurology — Fri, 20 Jan 2012 05:00:00 +0100

Authors: Sadan O, Shemesh N, Barzilay R, Dadon-Nahum M, Blumenfeld-Katzir T, Assaf Y, Yeshurun M, Djaldetti R, Cohen Y, Melamed E, Offen D Abstract Huntington's disease (HD) is a hereditary, progressive and ultimately fatal neurodegenerative disorder. Excitotoxicity and reduced availability of neurotrophic factors (NTFs) likely play roles in HD pathogenesis. Recently we developed a protocol that induces adult human bone marrow derived mesenchymal stem cells (MSCs) into becoming NTF secreting cells (NTF(+) cells). Striatal transplantation of such cells represents a promising autologous therapeutic approach whereby NTFs are delivered to damaged areas. Here, the efficacy of NTF(+) cells was evaluated using the quinolinic acid (QA) rat model for excitotoxicity. We show that NTF(+) cell...

Investigators achieve important step toward treating Huntington's disease

ScienceDaily Headlines — Thu, 19 Jan 2012 21:32:32 +0100

Researchers have developed a technique for using stem cells to deliver therapy that specifically targets the genetic abnormality found in Huntington's disease, a hereditary brain disorder that causes progressive uncontrolled movements, dementia and death. (Source: ScienceDaily Headlines)

UC Davis investigators achieve important step toward treating Huntington's disease

EurekAlert! - Medicine and Health — Thu, 19 Jan 2012 05:00:00 +0100

(University of California - Davis Health System) A team of researchers at the UC Davis Institute for Regenerative Cures has developed a technique for using stem cells to deliver therapy that specifically targets the genetic abnormality found in Huntington's disease, a hereditary brain disorder that causes progressive uncontrolled movements, dementia and death. (Source: EurekAlert! - Medicine and Health)

Neuronal Autophagy and Neurodegenerative Diseases.

exp Mol Med — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Son JH, Shim JH, Kim KH, Ha JY, Han JY Abstract Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autoph...

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Paraventricular nucleus neuropeptide expression in Huntington's disease patients

Brain Pathology — Wed, 18 Jan 2012 05:00:00 +0100

AbstractNeuroendocrine, metabolic and autonomic nervous system dysfunction are prevalent among patients with Huntington's disease (HD) and may underlie symptoms such as depression, weight loss and autonomic failure. Using post‐mortem paraffin embedded tissue, we assessed the integrity of the major neuropeptide populations in the paraventricular nucleus (PVN) ‐ the hypothalamic neuroendocrine and autonomic integration center ‐ in HD patients. The number corticotropin‐releasing hormone, cocaine‐ and amphetamine‐ regulated transcript, arginine vasopressin and oxytocin immunoreactive neurons did not differ between HD patients and control subjects. However, the significant positive correlation between arginine vasopressin and oxytocin immunoreactive neurons in control subjects (P = ...

Neurodegenerative disease: Preventing 'SIRTain' death by mutant huntingtin

Nature Reviews Neuroscience — Wed, 18 Jan 2012 05:00:00 +0100

Nature Reviews Neuroscience 13, 71 (2012). doi:10.1038/nrn3182 Author: Monica Hoyos Flight Two independent studies link mutant huntingtin to inactivation of the deacetylase enzyme SIRT1 and highlight a neuroprotective role for SIRT1 in mouse models of Huntington's disease. (Source: Nature Reviews Neuroscience)

Analysis of the parameters of oxidative stress in patients with Parkinson’s disease

Comparative Clinical Pathology — Tue, 17 Jan 2012 07:16:55 +0100

Abstract The increasing data provides enough evidences confirming the involvement of free radicals and other reactive oxygen species (ROS) superoxide radical ( . O2−), nitric oxide (NO . ), hydrogen peroxide (H2O2) and hydroxyl radicals ( . OH) in a number of physiological and pathological processes. Imbalance between levels of ROS resulting in the body and the capacity of antioxidant defense mechanisms occur oxidative stress (OS). OS is related to a number of structural and functional damages to cells and is involved in the pathogenesis of many diseases, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis, and Huntington disease. Defects in oxidative phosphorylation and oxidative damage play ...

Scripps research scientists create novel RNA repair technology

EurekAlert! - Biology — Tue, 17 Jan 2012 05:00:00 +0100

(Scripps Research Institute) Scientists from the Florida campus of the Scripps Research Institute have identified a compound that can help repair a specific type of defect in RNA, a type of genetic material. The methods in the new study could accelerate the development of therapeutics to treat a variety of incurable diseases such as Huntington's disease, Spinocerebellar ataxia, and Kennedy disease. (Source: EurekAlert! - Biology)

BioEssays 2/2012

BioEssays — Sun, 15 Jan 2012 10:47:20 +0100

The ERK signalling pathway and Huntington's disease. On pages 142–148 Bodai and Marsh discuss the complexity of MAPK signaling in Huntington's disease. In this neurodegenerative disorder, mutant huntingtin protein can both activate or inhibit the MAP kinase ERK depending on the cell type and state. These actions can impact intercellular BDNF‐ and glutamate‐signaling and other events that are transmitted through the ERK kinase pathway. Thus, pathogenic Htt can both activate and/or dampen different branches of the ERK cascade. Understanding the source of this complexity and ERK's key role in the pathogenic response may allow pharmacologic targeting that selectively enhances the protective branches of the ERK response for the treatment of this as yet incurable disease. (Source: BioEssay...

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Cyber-bullied girl with Huntington's Disease dies

Health News: CBSNews.com — Fri, 13 Jan 2012 17:50:18 +0100

9-year-old Kathleen Edwards taunted by former neighbor in 2010 died Wednesday (Source: Health News: CBSNews.com)

Using the Time-Varying Effect Model (TVEM) to Examine Dynamic Associations between Negative Affect and Self Confidence on Smoking Urges: Differences between Successful Quitters and Relapsers

Prevention Science — Fri, 13 Jan 2012 16:50:42 +0100

Abstract With technological advances, collection of intensive longitudinal data (ILD), such as ecological momentary assessments, becomes more widespread in prevention science. In ILD studies, researchers are often interested in the effects of time-varying covariates (TVCs) on a time-varying outcome to discover correlates and triggers of target behaviors (e.g., how momentary changes in affect relate to momentary smoking urges). Traditional analytical methods, however, impose important constraints, assuming a constant effect of the TVC on the outcome. In the current paper, we describe a time-varying effect model (TVEM) and its applications to data collected as part of a smoking-cessation study. Differentiating between groups of short-term successful quitters (N = 207) and...

ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease

Cell Death and Differentiation — Fri, 13 Jan 2012 05:00:00 +0100

Authors: J Lee, Y K Hong, G S Jeon, Y J Hwang, K Y Kim, K H Seong, M-K Jung, D J Picketts, N W Kowall, K S Cho & H Ryu (Source: Cell Death and Differentiation)

An open system for automatic home-cage behavioral analysis and its application to male and female mouse models of Huntington's disease.

Behavioural Brain Research — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Zarringhalam K, Ka M, Kook YH, Terranova J, Suh Y, King OD, Um M Abstract Changes in routine mouse home-cage behavioral activities have been used recently to study alterations of neural circuits caused by genetic and environmental modifications and by drug administration. Nevertheless, automatic assessment of mouse home-cage behaviors remains challenging due to the cost of proprietary systems and to the difficulty in adjusting systems to different monitoring conditions. Here we present software for the automatic quantification of multiple facets of mouse home-cage behaviors, suitable for continuous 24h video monitoring. We used this program to assess behavioral changes in male and female R6/2 transgenic mouse models of Huntington's disease over a 10-week period. Consistent...

Nucleic Acid-Based Therapy Approaches for Huntington's Disease

Computational Intelligence and Neuroscience — Thu, 12 Jan 2012 11:11:41 +0100

Huntington's disease (HD) is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to ...

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Coastal Commission fines Huntington Beach property owner $430,000

Los Angeles Times - Science — Thu, 12 Jan 2012 05:00:00 +0100

Goodell Family Trust also agrees to rebury artifacts and restore areas disturbed when archaeologists dug pits on family-owned land on the Bolsa Chica Mesa in 2010.State coastal regulators Wednesday criticized and fined a property owner for unearthing artifacts at a 9,000-year-old Native American village site near the Bolsa Chica wetlands in Huntington Beach. (Source: Los Angeles Times - Science)

Behavioural state differentially engages septohippocampal cholinergic and GABAergic neurons in R6/1 Huntington's disease mice.

Neurobiology of Learning and Memory — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Ransome MI, Hannan AJ Abstract Huntington's disease (HD) is a neurodegenerative condition characterised by progressive motor, psychological and cognitive decline. R6/1 HD transgenic mice model the clinical hippocampal-dependent cognitive deficits observed in patients. Cholinergic and GABAergic septohippocampal projections play important roles in hippocampal-dependent cognition. The current study examined neuronal activity of cholinergic and GABAergic septohippocampal projections in response to arousal elicited during differing behavioural states. The different behavioural states examined were; home cage (controls), acute exploration of a novel enriched environment and either spontaneous wakefulness (dark phase) or spontaneous sleep (light phase). We employed triple-label i...

Iron dysregulation in movement disorders.

Neurobiology of Disease — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Dusek P, Jankovic J, Le W Abstract Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism. Phospholipids are major constituents of myelin and iron accumulation has been linked to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzyme...

Diet counts: Iron intake in teen years can impact brain in later life

UCLA Newsroom: Health Sciences — Wed, 11 Jan 2012 22:08:00 +0100

Iron is a popular topic in health news. Doctors prescribe it for medical reasons, and it's available over the counter as a dietary supplement. And while it's known that too little iron can result in cognitive problems, it's also known that too much promotes neurodegenerative diseases. Now, researchers at UCLA have found that in addition to causing cognitive problems, a lack of iron early in life can affect the brain's physical structure as well. UCLA neurology professor Paul Thompson and his colleagues measured levels of transferrin, a protein that transports iron throughout the body and brain, in adolescents and discovered that these transferrin levels were related to detectable differences in both the brain's macro-structure and micro-structure when the adolescents reached ...

Probucol modulates oxidative stress and excitotoxicity in Huntington's disease models in vitro.

Brain Research Bulletin — Wed, 11 Jan 2012 05:00:00 +0100

In this study we evaluated the potential relationship between energetic impairment, excitotoxicity and oxidative stress in rat striatal slices exposed to quinolinic acid (QA; as an excitotoxic model), 3-nitropropionic acid (3-NP; as an inhibitor of mitochondrial succinate dehydrogenase), as well as a combined model produced by the co-administration of these two toxins at subtoxic concentrations. We took advantage of the direct antioxidant/scavenger properties of Probucol in order to investigate the role of reactive oxygen species (ROS) in mediating the toxicity of both compounds alone or in association. Experiments with MK-801 (a NMDA type glutamate receptor antagonist) and succinate (an energy precursor agent) were also performed in an attempt to better comprehend the mechanisms of damage...

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Computational Studies on Translocator Protein (tspo) and its Ligands.

Current Topics in Medicinal Chemistry — Tue, 10 Jan 2012 19:55:13 +0100

Authors: Ortore G, Tuccinardi T, Martinelli A Abstract The Translocator Protein (18 kDa) (TSPO), previously known as the peripheral benzodiazepine receptor, is widely expressed in glial cells and in peripheral tissues and is involved in a variety of biological processes: steroidogenesis, cell growth and differentiation, apoptosis induction, etc. TSPO basal expression is up-regulated in a number of human pathologies, including a variety of tumors and neuropathologies, such as gliomas and neurodegenerative disorders (Huntington's and Alzheimer's diseases), as well as in various forms of brain injury and inflammation. Furthermore, changes in TSPO receptor levels have been found in anxiety and mood disorders. Nowadays, considerable efforts have been focused on the identification of new...

Studies Identify Promising Genes And Small Molecules To Use Against Devastating Diseases

Health News from Medical News Today — Mon, 09 Jan 2012 08:00:00 +0100

Two related studies from Northwestern University offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis (ALS), cancer, cystic fibrosis and type 2 diabetes. To do its job properly within the cell, a protein first must fold itself into the proper shape. If it doesn't, trouble can result. More than 300 diseases have at their root proteins that misfold, aggregate and eventually cause cellular dysfunction and death... (Source: Health News from Medical News Today)

Truncated N-terminal huntingtin fragment with expanded-polyglutamine (htt552-100Q) suppresses brain-derived neurotrophic factor transcription in astrocytes.

Acta Biochimica et Biophysica Sinica — Mon, 09 Jan 2012 05:00:00 +0100

In this study, a glia HD model, using an adenoviral vector to express wild-type htt552 (htt552-18Q) and its mutation (htt552-100Q) in rat primary cortical astrocytes, was generated to investigate the influence of htt552 on the transcription of brain-derived neurotrophic factor (BDNF). Results from enzyme linked immunosorbent assay showed that the level of BDNF in astrocyte-conditioned medium was decreased in the astrocytes expressing htt552-100Q. Quantitative real-time polymerase chain reaction demonstrated that htt552-100Q reduced the transcripts of the BDNF III and IV, hence, repressed the transcription of BDNF. Furthermore, immunofluorescence showed that aggregates formed by htt552-100Q entrapped transcription factors cAMP-response element-binding protein and stimulatory protein 1, whic...

Soon after copulation has been completed, a pair of the damselfly Ischnura denticollis (male above, female below) remains in tandem. During copulation, the male removes the sperm the female received from previous copulations, and then transfers his own. Reproduced by permission of Dustin Huntington.

Ethology — Sat, 07 Jan 2012 11:46:51 +0100

(Source: Ethology)

New hope for diseases of protein folding such as Alzheimer’s, Parkinson’s diseases, ALS, cancer and diabetes

ScienceDaily Headlines — Fri, 06 Jan 2012 18:59:59 +0100

Two related studies offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, ALS, cystic fibrosis, cancer and type 2 diabetes. The research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development. (Source: ScienceDaily Headlines)

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Tiny worm points to big promise

EurekAlert! - Medicine and Health — Fri, 06 Jan 2012 05:00:00 +0100

(Northwestern University) Two related studies from Northwestern University offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, ALS, cystic fibrosis, cancer and type 2 diabetes. The research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development. (Source: EurekAlert! - Medicine and Health)

ProT{alpha} Interacts with mHtt and Reduces mHtt-caused Toxicity [Neurobiology]

Journal of Biological Chemistry — Fri, 06 Jan 2012 05:00:00 +0100

Huntington disease (HD), a fatal neurodegenerative disorder, is caused by a lengthening of the polyglutamine tract in the huntingtin (Htt) protein. Despite considerable effort, thus far there is no cure or treatment available for the disorder. Using the approach of tandem affinity purification we recently discovered that prothymosin-α (ProTα), a small highly acidic protein, interacts with mutant Htt (mHtt). This was confirmed by co-immunoprecipitation and a glutathione S-transferase (GST) pull-down assay. Overexpression of ProTα remarkably reduced mHtt-induced cytotoxicity in both non-neuronal and neuronal cell models expressing N-terminal mHtt fragments, whereas knockdown of ProTα expression in the cells enhanced mHtt-caused cell death. Deletion of the central acidic domain of ProTα ...

Brain Energy Deficit in Huntington Disease [Bioenergetics]

Journal of Biological Chemistry — Fri, 06 Jan 2012 05:00:00 +0100

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/...

Hsp90 Stabilizes Mutant Huntingtin [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 06 Jan 2012 05:00:00 +0100

Mechanisms to reduce the cellular levels of mutant huntingtin (mHtt) provide promising strategies for treating Huntington disease (HD). To identify compounds enhancing the degradation of mHtt, we performed a high throughput screen using a hippocampal HN10 cell line expressing a 573-amino acid mHtt fragment. Several hit structures were identified as heat shock protein 90 (Hsp90) inhibitors. Cell treatment with these compounds reduced levels of mHtt without overt toxic effects as measured by time-resolved Förster resonance energy transfer assays and Western blots. To characterize the mechanism of mHtt degradation, we used the potent and selective Hsp90 inhibitor NVP-AUY922. In HdhQ150 embryonic stem (ES) cells and in ES cell-derived neurons, NVP-AUY922 treatment substantially reduced solubl...

Finding a sirtuin truth in Huntington's disease

Nature Medicine — Fri, 06 Jan 2012 05:00:00 +0100

Nature Medicine 18, 24 (2012). doi:10.1038/nm.2624 Author: Albert R La Spada The search for compounds to treat neurodegenerative disorders is especially pressing given the rapidly growing elderly human population and has led to the consideration of sirtuin proteins as potential therapeutic candidates. Two studies now report that modulating the expression of the sirtuin Sirt1 has therapeutic benefit in Huntington's disease mouse models and identify putative downstream targets of Sirt1 involved in improved disease outcomes (pages 159–165 and 153–158). (Source: Nature Medicine)

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Rare Metabolic Diseases - New Treatment Approaches

Health News from Medical News Today — Thu, 05 Jan 2012 18:00:00 +0100

According to a study published in the December issue of Chemistry & Biology, a crucial interaction that could lead to a novel treatment for Fabry disease (a rare childhood metabolic disorder), has been discovered by an investigation team led by biochemist Scott Garman at the University of Massachusetts Amherst. In addition, the finding will researchers understand other protein-folding disorders, such as Parkinson's, Huntington's, and Alzheimer's diseases. Fabry disease is caused by the lack of or faulty alpha-galactosidase (Î±-GAL) enzyme needed to metabolize lipids... (Source: Health News from Medical News Today)

A dietary pattern derived to correlate with estrogens and risk of postmenopausal breast cancer

Breast Cancer Research and Treatment — Thu, 05 Jan 2012 06:51:44 +0100

In conclusion, diet pattern appeared to only have modest association with estrogens, and was not associated with postmenopausal breast cancer risk. Although these results were null, it should be repeated in other populations as differences in food intake may yield a dietary pattern with stronger association with estrogens. Content Type Journal ArticleCategory EpidemiologyPages 1-6DOI 10.1007/s10549-011-1942-zAuthors Teresa T. Fung, Department of Nutrition, Simmons College, 300 The Fenway, Boston, MA 02115, USAMatthias B. Schulze, Department of Molecular Epidemiology, German Institute of Nutrition, Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyFrank B. Hu, Department of Nutrition, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USASusan E. ...

A critical window of CAG repeat-length correlates with phenotype severity in the R6/2 mouse model of Huntington's disease

Journal of Neurophysiology — Wed, 04 Jan 2012 05:00:00 +0100

The R6/2 mouse is the most frequently used model for experimental and preclinical drug trials in Huntington's disease (HD). When the R6/2 mouse was first developed, it carried exon 1 of the huntingtin gene with ~150 cytosine-adenine-guanine (CAG) repeats. The model presented with a rapid and aggressive phenotype that shared many features with the human condition and was particularly similar to juvenile HD. However, instability in the CAG repeat length due to different breeding practices has led to both decreases and increases in average CAG repeat lengths among colonies. Given the inverse relationship in human HD between CAG repeat length and age at onset and to a degree, the direct relationship with severity of disease, we have investigated the effect of altered CAG repeat length. Four li...

New Treatment Direction For Rare Metabolic Diseases

Health News from Medical News Today — Tue, 03 Jan 2012 09:00:00 +0100

A research team led by biochemist Scott Garman at the University of Massachusetts Amherst has discovered a key interaction at the heart of a promising new treatment for a rare childhood metabolic disorder known as Fabry disease. The discovery will help understanding of other protein-folding disorders such as Alzheimer's, Parkinson's and Huntington's diseases, as well. Findings are featured as the cover story in the current issue of Chemistry & Biology... (Source: Health News from Medical News Today)

Do Persons with Diabetes Benefit from Combination Statin and Fibrate Therapy?

Current Cardiology Reports — Mon, 02 Jan 2012 16:57:10 +0100

Abstract Combination fibrate-statin therapy favorably modifies the atherogenic, triglyceride-rich lipoprotein environment, common to insulin resistance, diabetes, and higher cardiovascular disease (CVD) risk. Five major fibrate randomized clinical trial (RCT) results (HHS, VA-HIT, BIP, FIELD, and ACCORD-Lipid) demonstrated four consistent features: 1) the highest CVD event rates occurred in the placebo subgroups possessing atherogenic “moderate” dyslipidemia (triglycerides, > 200 mg/dL, and low high-density lipoprotein cholesterol [HDL-C], < 35–40 mg/dL); 2) with this subgroup having the greatest “hypothesis-generating” fibrate benefit (27% to 65% relative risk reduction, variable significance [P values ranging 0.057–0.005]); 3) those subgrou...

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Beyond the patient: The broader impact of genetic discrimination among individuals at risk of Huntington disease

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics — Sun, 01 Jan 2012 05:00:00 +0100

AbstractWe aimed to address gaps in current understanding of the scope and impact of discrimination, by examining a cohort of individuals at‐risk for Huntington disease (HD), to describe the prevalence of concern for oneself and one's family in multiple domains; strategies used to mitigate discrimination; and the extent to which concerns relate to experiences. We conducted a cross‐sectional survey of 293 individuals at‐risk for HD (80% response rate); 167 respondents were genetically tested and 66 were not. Fear of discrimination was widespread (86%), particularly in the insurance, family and social settings. Approximately half of concerned individuals experienced discrimination (40–62%, depending on genetic status). Concern was associated with “keeping quiet” about one's risk ...

Huntington's disease: Objective assessment of posture—A link between motor and functional deficits

Movement Disorders — Sun, 01 Jan 2012 05:00:00 +0100

Is It Alzheimer's or a Different Dementia?

About Alzheimers Disease — Sat, 31 Dec 2011 05:00:00 +0100

Alzheimer's is the most common form of dementia, but not the only one. I've had several conversations with people lately about other types of dementia. Here are a few I've chosen to highlight today. Take normal pressure hydrocephalus, for example. This potentially reversible condition is caused by the building up of cerebrospinal fluid in the brain. If the fluid is drained, symptoms sometimes improve. Or, how about frontotemporal dementia (FTD)? FTD is a term that groups several related dementias together, including Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia, Progressive Supranuclear Palsy and Corticobasal Degeneration. Sound confusing? These four types of frontotemporal dementia are all caused primarily by changes in the frontal and temporal lobes of the bra...

Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease.

Neurobiology of Aging — Sat, 31 Dec 2011 05:00:00 +0100

Authors: Griffioen KJ, Wan R, Brown TR, Okun E, Camandola S, Mughal MR, Phillips TM, Mattson MP Abstract Huntington's disease (HD) is associated with profound autonomic dysfunction including dysregulation of cardiovascular control often preceding cognitive or motor symptoms. Brain-derived neurotrophic factor (BDNF) levels are decreased in the brains of HD patients and HD mouse models, and restoring BDNF levels prevents neuronal loss and extends survival in HD mice. We reasoned that heart rate changes in HD may be associated with altered BDNF signaling in cardiovascular control nuclei in the brainstem. Here we show that heart rate is elevated in HD (N171-82Q) mice at presymptomatic and early disease stages, and heart rate responses to restraint stress are attenuated. BDNF levels wer...

In Huntington's Disease, Regulatory Enzyme Overexpression May Protect Against Neurodegeneration

Health News from Medical News Today — Fri, 30 Dec 2011 08:00:00 +0100

Treatment that increases brain levels of an important regulatory enzyme may slow the loss of brain cells that characterizes Huntington's disease (HD) and other neurodegenerative disorders. In a report receiving advance online publication in Nature Medicine, a Massachusetts General Hospital (MGH)-based research team reports that increased expression of Sirt1, one of a family of enzymes called sirtuins, in the brain of a mouse model of HD protected against neurodegeneration. They also identified a potential mechanism for this protective effect... (Source: Health News from Medical News Today)

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SPECT Study of the Nigrostriatal Dopaminergic System in Huntington's Disease

Journal of Neuroimaging — Fri, 30 Dec 2011 05:00:00 +0100

CONCLUSIONSWe showed that the postsynaptic part of the nigrostriatal pathway was involved. The presynaptic part is usually not affected but could occur in very advanced cases. Our findings suggest that SPECT imaging of D2 receptors is useful for diagnosing and monitoring HD.J Neuroimaging 2011;XX:1–5. (Source: Journal of Neuroimaging)

Talking Mats in a discussion group for people with Huntington's disease.

Disability and Rehabilitation. Assistive Technology. — Thu, 29 Dec 2011 05:00:00 +0100

Conclusions: TM could be useful in discussion groups for people with HD. An increased number of follow-up questions when TM is used may lead to a deeper understanding within the group. This study is the first of its kind and more research in the area is needed. [Box: see text]. PMID: 22204703 [PubMed - as supplied by publisher] (Source: Disability and Rehabilitation. Assistive Technology.)

Human platelet concentrates: a source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor.

Transfusion — Thu, 29 Dec 2011 05:00:00 +0100

CONCLUSION: We obtained a S/D-treated, highly enriched mature PLT-derived BDNF fraction that could help unveil the pharmacokinetics, pharmacodynamic, and potential therapeutic applications of the BDNF neurotrophin. PMID: 22211513 [PubMed - as supplied by publisher] (Source: Transfusion)

Brain Imaging May Provide New Biomarker of Huntington's DiseaseBrain Imaging May Provide New Biomarker of Huntington's Disease

Medscape Today Headlines — Wed, 28 Dec 2011 22:48:22 +0100

An objectively defined set of validated measures may enhance the efficacy of drug development. Medscape Medical News (Source: Medscape Today Headlines)

Alnylam Announces Publication of Pre-clinical Results with ALN-HTT, an RNAi Therapeutic for the Treatment of Huntington's Disease, in Experimental Neurology

Drugs.com - Pharma News — Wed, 28 Dec 2011 13:11:01 +0100

– Data Show Broad CNS Distribution and Robust Therapeutic Silencing of Gene Responsible for Huntington's Disease – CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec 28, 2011 - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading... (Source: Drugs.com - Pharma News)

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Induced pluripotent stem cell lines from Huntington's disease mice undergo neuronal differentiation while showing alterations in the lysosomal pathway.

Neurobiology of Disease — Wed, 28 Dec 2011 05:00:00 +0100

Authors: Castiglioni V, Onorati M, Rochon C, Cattaneo E Abstract Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an excessive expansion of a CAG trinucleotide repeat in the gene encoding the protein huntingtin, resulting in an elongated stretch of glutamines near the N-terminus of the protein. Here we report the derivation of a collection of 11 induced pluripotent stem (iPS) cell lines generated through somatic reprogramming of fibroblasts obtained from the R6/2 transgenic HD mouse line. We show that CAG expansion has no effect on reprogramming efficiency, cell proliferation rate, brain-derived neurotrophic factor level, or neurogenic potential. However, genes involved in the cholesterol biosynthesis pathway, which is altered in HD, are also ...

Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target

Nucleic Acids Research — Sun, 25 Dec 2011 05:00:00 +0100

We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases. (Source: Nucleic Acids Research)

MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway

Angiogenesis — Sat, 24 Dec 2011 16:45:49 +0100

Abstract Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation of primary human microvas...

Gene therapy for Huntington's disease.

Neurobiology of Disease — Sat, 24 Dec 2011 05:00:00 +0100

Authors: Ramaswamy S, Kordower JH Abstract Huntington's disease (HD) is a neurodegenerative disease for which there is no cure. Therapies that are efficacious in animal models have to date shown no benefit for humans. One potential powerful approach is gene therapy. The ideal method of administration of gene therapy has been hotly debated and viral vectors have provided one method of long-term and wide-spread delivery to the brain. Trophic factors to protect cells from degeneration and RNAi to reduce mutant huntingtin (mHtt) protein expression are 2 main classes of compounds that demonstrate benefit in animal models. This review will examine some commonly used adeno-associated viral (AAV) vectors and discuss some therapies that hold promise for HD. PMID: 22222669 [PubMed - as s...

Neurite transection produces cytosolic oxidation, which enhances plasmalemmal repair

Journal of Neuroscience Research — Sat, 24 Dec 2011 00:47:02 +0100

AbstractTo survive, cells must rapidly repair (seal) plasmalemmal damage. Cytosolic oxidation has been shown to increase cell survival in some cases and produce cell death in other protocols. An antioxidant (melatonin; Mel) has been reported to decrease the probability of sealing plasmalemmal damage. Here we report that plasmalemmal damage produces cytosolic oxidation, as assayed by methylene blue (MB) color change in rat B104 hippocampal cells. Plasmalemmal sealing is affected by duration of Ca2+ deprivation and length of exposure to, and concentration of, oxidizing agents such as H2O2 and thimerosal (TH). Cytosolic oxidation by 10 μM to 50 mM H2O2 or 100 μM to 2 mM TH increases the probability of Ca2+‐dependent plasmalemmal sealing, whereas higher concentrations of H2O2 decrease seal...

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New Treatment Direction For Rare Metabolic Diseases

Health News from Medical News Today — Fri, 23 Dec 2011 09:00:00 +0100

Poly(Q) Aggregation Causes Free Radical Production [Neurobiology]

Journal of Biological Chemistry — Fri, 23 Dec 2011 05:00:00 +0100

Neurodegenerative diseases are characterized by intra- and/or extracellular protein aggregation and oxidative stress. Intense attention has been paid to whether protein aggregation itself contributes to abnormal production of free radicals and ensuing cellular oxidative damage. Although this question has been investigated in the context of extracellular protein aggregation, it remains unclear whether protein aggregation inside cells alters the redox homeostasis. To address this, we have used in vitro and in vivo (cellular) models of Huntington disease, one of nine polyglutamine (poly(Q)) disorders, and examined the causal relationship among intracellular protein aggregation, reactive oxygen species (ROS) production, and toxicity. Live imaging of cells expressing a fragment of huntingtin (h...

GDNF and GDNFOS Isoforms in Alzheimer Disease [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 23 Dec 2011 05:00:00 +0100

Primate-specific genes and isoforms could provide insight into human brain diseases. Our bioinformatic analysis revealed that there are possibly five isoforms of human GDNF gene with different pre- and pro-regions by inter- and intra-exon splicing. By using TaqMan primer probe sets, designed between exons, we verified the expression of all isoforms. Furthermore, a novel GDNFOS gene was found to be transcribed from the opposite strand of GDNF gene. GDNFOS gene has four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are long noncoding RNAs, and GDNFOS3 encodes a protein of 105 amino acids. To study human GDNF and GDNFOS regulation in neurodegenerative diseases, the protein and mRNA levels were measured by Western blot and RT-quantitative PCR, respectively, in postmortem ...

Unbalance of CB1 receptors expressed in GABAergic and glutamatergic neurons in a transgenic mouse model of Huntington's disease.

Neurobiology of Disease — Fri, 23 Dec 2011 05:00:00 +0100

Authors: Chiodi V, Uchigashima M, Beggiato S, Ferrante A, Armida M, Martire A, Potenza RL, Ferraro L, Tanganelli S, Watanabe M, Domenici MR, Popoli P Abstract Cannabinoid CB1 receptors (CB1Rs) are known to be downregulated in patients and in animal models of Huntington's disease (HD). However, the functional meaning of this reduction, if any, is still unclear. Here, the effects of the cannabinoid receptor agonist WIN 55,212-2 (WIN) were investigated on striatal synaptic transmission and on glutamate and GABA release in symptomatic R6/2 mice, a genetic model of HD. The expression levels of CB1Rs in glutamatergic and GABAergic synapses were also evaluated. We found that in R6/2 mice, WIN effects on synaptic transmission and glutamate release were significantly increased with respect ...

Biochemists develop promising new treatment direction for rare metabolic diseases

EurekAlert! - Medicine and Health — Thu, 22 Dec 2011 05:00:00 +0100

(University of Massachusetts at Amherst) A research team led by biochemist Scott Garman at the University of Massachusetts Amherst has discovered a key interaction at the heart of a promising new treatment for a rare childhood metabolic disorder known as Fabry disease. The discovery will help understanding of other protein-folding disorders such as Alzheimer's, Parkinson's and Huntington's diseases, as well. Findings are featured as the cover story in the current issue of Chemistry & Biology. (Source: EurekAlert! - Medicine and Health)

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Diversity, biogenesis and function of microbial amyloids.

Trends in Microbiology — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Blanco LP, Evans ML, Smith DR, Badtke MP, Chapman MR Abstract Amyloid is a distinct β-sheet-rich fold that many proteins can acquire. Frequently associated with neurodegenerative diseases in humans, including Alzheimer's, Parkinson's and Huntington's diseases, amyloids are traditionally considered the product of protein misfolding. However, the amyloid fold is now recognized as a ubiquitous part of normal cellular biology. Functional amyloids have been identified in nearly all facets of cellular life, with microbial functional amyloids leading the way. Unlike disease-associated amyloids, functional amyloids are assembled by dedicated, directed pathways and ultimately perform a physiological function that benefits the organism. The evolved amyloid assembly and disassembly ...

Researchers Slow Progression Of Huntington's Disease In Mouse Models

Health News from Medical News Today — Mon, 19 Dec 2011 09:00:00 +0100

Working with genetically engineered mice, Johns Hopkins researchers have discovered that a gene (SIRT1) linked to slowing the aging process in cells also appears to dramatically delay the onset of Huntington's disease (HD) and slow the progression of the relentless neurodegenerative disorder. HD in humans is a rare, fatal disorder caused by a mutation in a single gene and marked by progressive brain damage. Symptoms, which typically first appear in midlife, include jerky twitch-like movements, coordination troubles, psychiatric disorders and dementia... (Source: Health News from Medical News Today)

Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, protects dopaminergic neurons from neurotoxin‐induced damage

British Journal of Pharmacology — Mon, 19 Dec 2011 06:39:13 +0100

CONCLUSION AND IMPLICATIONS The novel neurotrophic and neuroprotective effects of SAHA demonstrated in this study suggest that further study of this HDAC inhibitor could provide a new therapeutic approach to the treatment of neurodegenerative diseases. (Source: British Journal of Pharmacology)

Protein aggregates in Huntington's disease.

Experimental Neurology — Mon, 19 Dec 2011 05:00:00 +0100

Authors: Arrasate M, Finkbeiner S Abstract Huntington's disease (HD) is an incurable neurodegenerative disease characterized by abnormal motor movements, personality changes, and early death. HD is caused by a mutation in the IT-15 gene that expands abnormally the number of CAG nucleotide repeats. As a result, the translated protein huntingtin contains disease-causing expansions of glutamines (polyQ) that make it prone to misfold and aggregate. While the gene and mutations that cause HD are known, the mechanisms underlying HD pathogenesis are not. Here we will review the state of knowledge of HD, focusing especially on a hallmark pathological feature-intracellular aggregates of mutant Htt called inclusion bodies (IBs). We will describe the role of IBs in the disease. We speculate t...

Regulatory enzyme overexpression may protect against neurodegeneration in Huntington's disease

EurekAlert! - Medicine and Health — Sun, 18 Dec 2011 05:00:00 +0100

(Massachusetts General Hospital) Treatment that increases brain levels of an important regulatory enzyme may slow the loss of brain cells that characterizes Huntington's disease (HD) and other neurodegenerative disorders. A Massachusetts General Hospital-based research team found that increased expression of Sirt1, one of a family of enzymes called sirtuins, in the brain of a mouse model of HD protected against neurodegeneration. The investigators also identified a potential mechanism for this protective effect. (Source: EurekAlert! - Medicine and Health)

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Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets

Nature Medicine — Sun, 18 Dec 2011 05:00:00 +0100

Authors: Mali Jiang, Jiawei Wang, Jinrong Fu, Lin Du, Hyunkyung Jeong, Tim West, Lan Xiang, Qi Peng, Zhipeng Hou, Huan Cai, Tamara Seredenina, Nicolas Arbez, Shanshan Zhu, Katherine Sommers, Jennifer Qian, Jiangyang Zhang, Susumu Mori, X William Yang, Kellie L K Tamashiro, Susan Aja, Timothy H Moran, Ruth Luthi-Carter, Bronwen Martin, Stuart Maudsley, Mark P Mattson, Robert H Cichewicz, Christopher A Ross, David M Holtzman, Dimitri Krainc & Wenzhen Duan Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HTT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice). We now report t...

Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway

Nature Medicine — Sun, 18 Dec 2011 05:00:00 +0100

Authors: Hyunkyung Jeong, Dena E Cohen, Libin Cui, Andrea Supinski, Jeffrey N Savas, Joseph R Mazzulli, John R Yates, Laura Bordone, Leonard Guarente & Dimitri Krainc Sirt1, a NAD-dependent protein deacetylase, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. Here we show that Sirt1 has a neuroprotective role in models of Huntington's disease, an inherited neurodegenerative disorder caused by a glutamine repeat expansion in huntingtin protein (HTT). Brain-specific knockout of Sirt1 results in exacerbation of brain pathology in a mouse model of Huntington's disease, whereas overexpression of Sirt1 improves survival, neuropathology and the expression of brain-derived neurotrophic factor (BDNF) in Huntington's disease mice. We ...

Interaction between pathogenic proteins in neurodegenerative disorders.

J Cell Mol Med — Fri, 16 Dec 2011 05:00:00 +0100

Authors: Jellinger KA Abstract The misfolding and progressive aggregation of specific proteins in selective regions of the nervous system is a seminal occurrence in many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, increasing evidence indicates considerable overlap between synucleinopathies, tauopathies and other protein-misfolding diseases. Inclusions, often characteristic hallmarks of these disorders, suggest interactions of pathological proteins enganging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Alzheimer, Parkinso...

Age, CAG repeat length, and clinical progression in Huntington's disease

Movement Disorders — Thu, 15 Dec 2011 05:00:00 +0100

The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow‐up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini‐Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repea...

Extraordinary Nonlinear Absorption in 3D Bowtie Nanoantennas

Nano Letters — Tue, 13 Dec 2011 14:18:27 +0100

Nano LettersDOI: 10.1021/nl2034915 (Source: Nano Letters)

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[Comment] TRACK-HD: both promise and disappointment

Lancet Neurology — Tue, 13 Dec 2011 14:12:14 +0100

The frustrations and disappointments associated with the failure to identify disease-modifying drugs for neurodegenerative diseases have been particularly acute for the Huntington's disease (HD) patient and research communities. Many promising drug candidates for HD with biological plausibility and preliminary successes in small studies have floundered once assessed in the gold-standard arena of large, randomised, double-blind, placebo-controlled trials, as have drugs for Alzheimer's and Parkinson's diseases. (Source: Lancet Neurology)

[Articles] Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: analysis of 24 month observational data

Lancet Neurology — Tue, 13 Dec 2011 14:12:14 +0100

In this report we define a battery of potential outcome measures for therapeutic trials.MethodsWe assessed longitudinal data collected at baseline, 12 months, and 24 months at sites in Leiden (Netherlands), London (UK), Paris (France), and Vancouver (Canada). Participants were individuals without HD but carrying the mutant HTT gene (ie, premanifest HD), patients with early HD, and healthy control individuals matched by age and sex to the combined HD groups. (Source: Lancet Neurology)

Recent advances in the development of tissue transglutaminase (TG2) inhibitors.

Amino Acids — Tue, 13 Dec 2011 05:00:00 +0100

Authors: Badarau E, Collighan RJ, Griffin M Abstract Tissue transglutaminase (TG2) is a Ca(2+)-dependent enzyme and probably the most ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays a number of important roles in a variety of biological processes. Via its transamidating function, it is responsible for the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. Intracellularly, Ca(2+) activation of the enzyme is normally tightly regulated by the binding of GTP. However, upregulated levels of TG2 are associated with many disease states like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple sclerosis, Alzheimer's, Huntington's and Parkinson's disease. Selective inhibitors for TG2 both cell ...

Massive choroidal effusion and painful secondary glaucoma from underlying uveal melanoma

Graefe's Archive for Clinical and Experimental Ophthalmology — Mon, 12 Dec 2011 06:33:10 +0100

Content Type Journal ArticleCategory Case ReportPages 1-4DOI 10.1007/s00417-011-1881-8Authors Juan C. Iturralde, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USACarlos Bianciotto, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USASara E. Lally, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USAMichael Krasnow, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USACarol L. Shields, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USA Journal Graefe's Archive for Clinical and Experimental OphthalmologyOnline ISSN 1435-702XPrint ISSN 0721-832X (Source: Graefe's Archive for Clinic...

Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease.

Neurobiology of Disease — Sun, 11 Dec 2011 05:00:00 +0100

Authors: Liu R, Lei JX, Luo C, Lan X, Chi L, Deng P, Lei S, Ghribi O, Liu QY Abstract Though loss of function in CBP/p300, a family of CREB-binding proteins, has been causally associated with a variety of human neurological disorders, such as Rubinstein-Taybi syndrome, Huntington's disease and drug addiction, the role of EP300 interacting inhibitor of differentiation 1 (EID1), a CBP/p300 inhibitory protein, in modulating neurological functions remains completely unknown. Through the examination of EID1 expression and cellular distribution, we discovered that there is a significant increase of EID1 nuclear translocation in the cortical neurons of Alzheimer's disease (AD) patient brains compared to that of control brains. To study the potential effects of EID1 on neurological functio...

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Intergenerational instability in Huntington disease: Extreme repeat changes among 134 transmissions

Movement Disorders — Fri, 09 Dec 2011 05:00:00 +0100

(Source: Movement Disorders)

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease

Movement Disorders — Fri, 09 Dec 2011 05:00:00 +0100

The ethics of disclosing genetic diagnosis for Alzheimer's disease: do we need a new paradigm?

British Medical Bulletin — Thu, 08 Dec 2011 05:00:00 +0100

Introduction or background Genetic testing for rare Mendelian disorders represents the dominant ethical paradigm in clinical and professional practice. Predictive testing for Huntington's disease is the model against which other kinds of genetic testing are evaluated, including testing for Alzheimer's disease. Sources of data This paper retraces the historical development of ethical reasoning in relation to predictive genetic testing and reviews a range of ethical, sociological and psychological literature from the 1970s to the present. Areas of agreement In the past, ethical reasoning has embodied a distinct style whereby normative principles are developed from a dominant disease exemplar. Areas of controversy This reductionist approach to formulating ethical frameworks breaks down in ...

The Huntington's Disease health-related Quality of Life questionnaire (HDQoL): A disease-specific measure of health-related quality of life.

Clinical Genetics — Thu, 08 Dec 2011 05:00:00 +0100

Authors: Hocaoglu MB, Gaffan EA, Ho AK Abstract Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive and psychiatric disturbances, and yet there is no disease-specific patient-reported health-related quality of life outcome measure for patients. Our aim was to develop and validate such an instrument, i.e., the Huntington's Disease health-related Quality of Life questionnaire (HDQoL), to capture the true impact of living with this disease. Semi-structured interviews were conducted with the full spectrum of people living with Huntington's, to form a pool of items, which were then examined in a larger sample prior to data-driven item reduction. We provide the statistical basis for the extraction of three different sets of scales from the ...

Tetrabenazine: For Chorea Associated with Huntingtons Disease

CNS Drugs — Wed, 07 Dec 2011 13:56:22 +0100

(Source: CNS Drugs)

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Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and CNS infection: to die or not to die – that is the question

Clinical and Experimental Immunology — Wed, 07 Dec 2011 05:00:00 +0100

AbstractDeath rules our lives. In this short review, we summarise new insights into molecular mechanisms of neurodegeneration. Here we review the most important processes of cell death: apoptosis and oncosis. We focus on autophagy, which is pivotal for neuronal homeostasis, in the context of neurodegeneration, infection and immunity. Its dysfunction has been linked to several neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer diseases. Our understanding is still incomplete but may highlight attractive new avenues for the development of treatment strategies to combat neurodegenerative diseases. (Source: Clinical and Experimental Immunology)

Vitamin C transport and its role in the central nervous system.

Sub-Cellular Biochemistry — Sun, 04 Dec 2011 18:56:15 +0100

Authors: May JM Abstract Vitamin C, or ascorbic acid, is important as an antioxidant and participates in numerous cellular functions. Although it circulates in plasma in micromolar concentrations, it reaches millimolar concentrations in most tissues. These high ascorbate cellular concentrations are thought to be generated and maintained by the SVCT2 (Slc23a2), a specific transporter for ascorbate. The vitamin is also readily recycled from its oxidized forms inside cells. Neurons in the central nervous system (CNS) contain some of the highest ascorbic acid concentrations of mammalian tissues. Intracellular ascorbate serves several functions in the CNS, including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxic...

Huntington's Disease: Two-Year Observational Follow-Up of Executive Function Evaluation with CNS Vital Signs Test in an Adult Patient

Infectious Diseases in Obstetrics and Gynecology — Sun, 04 Dec 2011 16:16:26 +0100

Conclusion. The tests may be useful to reveal the exact measure of the current evolutionary stage of HD patients, allowing for more efficient planning of treatment and future procedures, such as the medication, therapy, and physical activity to be administered. (Source: Infectious Diseases in Obstetrics and Gynecology)

Brain Measures May Help Design Huntington's Trials (CME/CE)

MedPage Today Public Health — Sat, 03 Dec 2011 23:13:13 +0100

(MedPage Today) -- Several objective outcome measures may help in designing trials of possible treatments for Huntington's disease, according to the results of a longitudinal study. (Source: MedPage Today Public Health)

Study Identifies Most Effective Ways To Assess Progression In Huntington's Disease, Which Could Speed Up Development Of Disease-modifying Drugs

Health News from Medical News Today — Fri, 02 Dec 2011 17:00:00 +0100

Researchers have identified a set of objective, validated measures for evaluating new treatments for Huntington's disease (HD) in phase 2 and 3 clinical trials. According to the researchers, whose findings have been published Online first in The Lancet Neurology, the discovery should increase future new drug trial's chances of success to delay onset and reduce the severity of HD... (Source: Health News from Medical News Today)

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Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases

Nature Reviews Drug Discovery — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Daniel W. Neef, Alex M. Jaeger & Dennis J. Thiele Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and prion-based neurodegeneration are associated with the accumulation of misfolded proteins, resulting in neuronal dysfunction and cell death. However, current treatments for these diseases predominantly address disease symptoms, rather than the underlying (Source: Nature Reviews Drug Discovery)

Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study

Journal of Psychopharmacology — Thu, 01 Dec 2011 05:00:00 +0100

Huntington’s disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 ...

Tetmodis 25mg tablets (Tetrabenazine)- New Product

NeLM - SPC Changes — Thu, 01 Dec 2011 05:00:00 +0100

Source: eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes Please refer to the link below for the New SPC for new product Tetmodis (tetrabenazine). It is indicated for hyperkinetic motor disorders with Huntington's chorea. (Source: NeLM - SPC Changes)

The Wilson films — Huntington's Chorea

Movement Disorders — Thu, 01 Dec 2011 05:00:00 +0100

AbstractWilson's Queen Square Case 9 with Huntington's chorea shows a 68‐year‐old man with mild to moderate generalized chorea, impaired fixation, and probable cognitive decline in keeping with a diagnosis of Huntington's disease (HD). An age of onset in the late sixties and a negative family history suggest a relatively small expanded trinucleotide repeat in the HTT gene in the patient and reduced penetrance of an even shorter repeat allele in one of his parents. A highly sensitive and specific gene test has been offered worldwide for diagnostic testing of HD for almost two decades. This test, obviously unavailable at Wilson's times, became the historic frontrunner for guidelines of symptomatic, presymptomatic, and prenatal testing for an adult‐onset neurodegenerative disorder. Rega...

Interaction between pathogenic proteins in neurodegenerative disorders

Journal of Cellular and Molecular Medicine — Thu, 01 Dec 2011 05:00:00 +0100

AbstractThe misfolding and progressive aggregation of specific proteins in selective regions of the nervous system is a seminal occurrence in many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, increasing evidence indicates considerable overlap between synucleinopathies, tauopathies and other protein‐misfolding diseases. Inclusions, often characteristic hallmarks of these disorders, suggest interactions of pathological proteins enganging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Alzheimer, Parkinson, Huntington, and prion dise...

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A role for immunophilins in cellular signalling in health and disease.

Current Medicinal Chemistry — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Rosado JA, Redondo PC Abstract Tissue and organ transplantation constitute the main medical advances of the last century, and has been possible thanks to the contribution of doctors like Loix Roux, who, in 1885, firstly described a technique consisting on tissue culture ex vivo, or Emerich Ullman and Max Lederer, whose publications in 1914 collected all preliminary surgical advances in the field. These pioneers soon realized the need to avoid the interference of the immunological system in order to obtain successful allotropic organ transplantation. At the beginning of the 80´s, cyclosporin (CsA), previously isolated and characterized in 1969 from the fungus Tolypocladium inflatum, became a miracle treatment to avoid organ rejection. After its discovery as an effective im...

In Mouse Model Dantrolene Protects Neurons From Huntington's Disease

Health News from Medical News Today — Mon, 28 Nov 2011 08:00:00 +0100

Huntington's disease (HD) is characterized by ongoing destruction of specific neurons within the brain. It affects a person's ability to walk, talk, and think - leading to involuntary movement and loss of muscle co-ordination. New research published in BioMed Central's open access journal Molecular Neurodegeneration shows that the RyanR inhibitor Dantrolene is able to reduce the severity of walking and balance problems in a mouse model of HD... (Source: Health News from Medical News Today)

Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity.

European Journal of Pharmacology — Mon, 28 Nov 2011 05:00:00 +0100

Authors: Kumar P, Kalonia H, Kumar A Abstract Huntington's disease is a progressive neurodegenerative disorder that gradually reduces memory, cognitive skills and normal movements of affected individuals. Systemic administration of 3-Nitropropionic acid induces selective striatal lesions in rodents and non-human primates. Therefore, the present study has been designed to elucidate the comparative mechanistic profile of gabapentin, lamotrigine and their interactions with GABAergic modulators against 3-Nitropropionic acid induced neurotoxicity. Systemic 3-Nitropropionic acid (10mg/kg) administration for 14days significantly reduced body weight, locomotor activity, grip strength, oxidative defense (LPO, nitrite, SOD and catalase) and impaired mitochondrial complex enzyme (I, II, IV an...

Dantrolene is neuroprotective in Huntingtons disease transgenic mouse model

Molecular Neurodegeneration — Fri, 25 Nov 2011 05:00:00 +0100

Dantrolene, a RyanR inhibitor and calcium signalling stabilizer, is identified as a potential agent for the treatment of Huntingdons Disease, further implicating the disturbance of intracellular calcium signalling in the pathogenesis of polyglutamine expansion diseases. (Source: Molecular Neurodegeneration)

Shrinking, widening, reversing, and stagnating trends in US socioeconomic inequities in cancer mortality for the total, black, and white populations: 1960–2006

Cancer Causes and Control — Thu, 24 Nov 2011 17:48:46 +0100

Conclusions The hypothesis that cancer mortality inequities are bound to increase is refuted by long-term data on total and site-specific cancer mortality stratified by socioeconomic position and race/ethnicity. Content Type Journal ArticleCategory Original paperPages 1-23DOI 10.1007/s10552-011-9879-4Authors Nancy Krieger, Department of Society, Human Development and Health (SHDH), Harvard School of Public Health (HSPH), 677 Huntington Avenue, Kresge 717, Boston, MA 02115, USAJarvis T. Chen, Department of Society, Human Development and Health (SHDH), Harvard School of Public Health (HSPH), 677 Huntington Avenue, Kresge 717, Boston, MA 02115, USAAnna Kosheleva, Department of Society, Human Development and Health (SHDH), Harvard School of Public Health (HSPH), 677 Hunt...

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Scavenger receptors and β-glucan receptors participate in the recognition of yeasts by murine macrophages

Inflammation Research — Thu, 24 Nov 2011 17:45:01 +0100

Conclusions Our results revealed that SRs belong to a redundant system of receptors for yeasts. Binding of yeasts to different receptors in resting versus CpG-ODN-pre-exposed macrophages may differentially affect polarization of adaptive immune responses. Content Type Journal ArticleCategory Original Research PaperPages 1-14DOI 10.1007/s00011-011-0395-5Authors Szczepan Józefowski, Department of Immunology, Jagiellonian University Medical College, 18 Czysta Street, 31-121 Kraków, PolandZhiping Yang, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USAJanusz Marcinkiewicz, Department of Immunology, Jagiellonian University Medical College, 18 Czysta Street, 31-121 Kraków, PolandLester ...

Dantrolene protects neurons from Huntington's disease

EurekAlert! - Medicine and Health — Thu, 24 Nov 2011 05:00:00 +0100

(BioMed Central) Huntington's disease is characterized by ongoing destruction of specific neurons within the brain. It affects a person's ability to walk, talk, and think - leading to involuntary movement and loss of muscle co-ordination. New research published in BioMed Central's open access journal Molecular Neurodegeneration shows that the RyanR inhibitor Dantrolene is able to reduce the severity of walking and balance problems in a mouse model of HD. (Source: EurekAlert! - Medicine and Health)

Re-conceptualising depression: what are today's most promising research leads? Where will the next breakthroughs come from? (2011-12-12)

Institute of Psychiatry | Events — Thu, 24 Nov 2011 02:31:12 +0100

ABSTRACT: Depression is a term used to group diverse syndromic presentations representing varied combinations of genes-environmental-brain interactions. From structural brain lesions such as those seen in stroke, Parkinson’s and Huntington’s diseases to harder to identify "functional defects" typically seen in younger patients, we are faced with combinations of pred (Source: Institute of Psychiatry | Events)

Perspectives of staff providing care at the end of life for people with progressive long-term neurological conditions.

Palliative and Supportive Care — Wed, 23 Nov 2011 17:49:32 +0100

This article examines the views and opinions of staff from a larger study exploring the palliative and end-of-life care needs of patients with progressive long-term neurological conditions (PLTNC).Method:Eighty staff, in a range of professions from three types of care services provided to people with PLTNC in England, took part in 14 focus groups and 3 individual interviews. Sites included six long-term residential neurological care centers, an inpatient service at an urban hospice, and a multi-disciplinary outpatient service for people with Huntington's disease.Results:Findings show a concordance between the views of staff from across the three types of participating services. Staff placed particular emphasis on teamwork, support from community-based resources, and developing rapport with...

Palmitoylation and trafficking of GAD65 is impaired in a cellular model of Huntington disease

BJ Cell — Mon, 21 Nov 2011 05:00:00 +0100

This study focuses on the effect of mhtt on the subcellular localization of glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing GABA. In this study, we report that the subcellular distribution of GAD is significantly altered in two neuronal cell lines that express either the N-terminus or full length mhtt. GAD65 is predominantly associated with Golgi membrane in cells expressing normal htt. However, it diffuses in the cytosol of cells expressing mhtt. As a result, vesicle-associated GAD65 trafficking is impaired. Since palmitoylation of GAD65 is required for GAD65 trafficking, we then demonstrate that palmitoylation of GAD65 is reduced in the HD model. Furthermore, overexpression of huntingtin-interacting protein 14, the enzyme responsible for palmitoylating GAD65 in...

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Palmitoylation and trafficking of GAD65 is impaired in a cellular model of Huntington disease.

The Biochemical Journal — Mon, 21 Nov 2011 05:00:00 +0100

Palmitoylation and trafficking of GAD65 is impaired in a cellular model of Huntington's disease

BJ Cell — Mon, 21 Nov 2011 05:00:00 +0100

Widespread suppression of huntingtin with convection-enhanced delivery of siRNA.

Experimental Neurology — Sat, 19 Nov 2011 05:00:00 +0100

Authors: Stiles D, Zhang Z, Ge P, Nelson B, Grondin R, Ai Y, Hardy P, Nelson PT, Guzaev AP, Butt MT, Charisse K, Kosovrasti V, Tchangov L, Meys M, Maier M, Nechev L, Manoharan M, Kaemmerer WF, Gwost D, Stewart GR, Gash DM, Sah DW Abstract Huntington's disease is an autosomal dominant neurodegenerative disease caused by a toxic gain of function mutation in the huntingtin gene (Htt). Silencing of Htt with RNA interference using direct CNS delivery in rodent models of Huntington's disease has been shown to reduce pathology and promote neuronal recovery. A key translational step for this approach is extension to the larger non-human primate brain, achieving sufficient distribution of small inhibitory RNA targeting Htt (siHtt) and levels of Htt suppression that may have therapeutic bene...

iTech Medical Shareholders Restructure the Board of Directors

Medical News (via PRIMEZONE) — Fri, 18 Nov 2011 16:04:00 +0100

HUNTINGTON BEACH, Calif., Nov. 18, 2011 (GLOBE NEWSWIRE) -- iTech Medical, Inc. (OTCBB:IMSU) (FWB:0IM), a medical information technology company, announced today that effective immediately the Board of Directors will be led by its CEO, and now Board Chairman, Mr. Warren G. Baker. Additionally, the company added three new members and returned a former member to the Board of Directors. (Source: Medical News (via PRIMEZONE))

The Eye Of The Fly: Researchers Discover Possible Key To Degenerative Nerve Diseases

Health News from Medical News Today — Fri, 18 Nov 2011 10:00:00 +0100

Researchers at the University of Wisconsin-Madison and collaborators have discovered a powerful new protein in the eye of the fruit fly that may shed light on blinding diseases and other sensory problems in humans. Reporting in the Nov. 16, 2011, issue of Neuron, the scientists note that similar but yet- to-be-identified proteins in the eye and brain could help explain age-related macular degeneration and retinitis pigmentosa, as well as Huntington's, Parkinson's, Alzheimer's and prion diseases... (Source: Health News from Medical News Today)

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Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy

Human Brain Mapping — Fri, 18 Nov 2011 05:00:00 +0100

AbstractTRACK‐HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3‐Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross‐sectional data from this large well‐characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene‐positive subjects (120 PreHD and 119 early HD) from the TRACK‐HD study were included. Using voxel‐based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, me...

Coordinated multidisciplinary care for ambulatory Huntington's disease patients. Evaluation of 18 months of implementation.

Orphanet Journal of Rare Diseases — Fri, 18 Nov 2011 05:00:00 +0100

Conclusions. We concluded that coordinating outreaching multidisciplinary care from an outpatient clinic into the dwelling place of the patient is feasible and appreciated. (Source: Orphanet Journal of Rare Diseases)

Rate of change in early Huntington's disease: A clinicometric analysis

Movement Disorders — Thu, 17 Nov 2011 05:00:00 +0100

AbstractSensitive outcome measures for patients with Huntington's disease (HD) are required for future clinical trials. Longitudinal data were collected from a 3‐year study of 379 patients suffering from early HD who were not treated by antipsychotics. Progression of UHDRS item scores was evaluated by linear regression and slope, whereas correlation coefficient, standard error, and P values were estimated on the basis of the data of eight evaluations from screening to study end (36 months). For the functional assessment dimension, the proportion of “no” responses at baseline and at study end was determined. Linear progression was observed for the motor score and for all three functional measures (i.e., functional assessment score, independence assessment score, and total functional c...

[Articles] Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial

Lancet Neurology — Thu, 17 Nov 2011 04:38:50 +0100

SummaryBackgroundHuntington's disease is a progressive neurodegenerative disorder, characterised by motor, cognitive, and behavioural deficits. Pridopidine belongs to a new class of compounds known as dopaminergic stabilisers, and results from a small phase 2 study in patients with Huntington's disease suggested that this drug might improve voluntary motor function. We aimed to assess further the effects of pridopidine in patients with Huntington's disease.MethodsWe undertook a 6 month, randomised, double-blind, placebo-controlled trial to assess the efficacy of pridopidine in the treatment of motor deficits in patients with Huntington's disease. (Source: Lancet Neurology)

[Comment] Pridopidine in treatment of Huntington's disease: beyond chorea?

Lancet Neurology — Thu, 17 Nov 2011 04:38:49 +0100

Huntington's disease is a neurodegenerative disorder for which new treatments are desperately needed. The disease results in abnormalities of behaviour, cognition, and movement. Although it has been widely viewed as primarily a movement disorder (eg, George Huntington's original paper describing the disease was entitled “On chorea”), the behavioural and cognitive features probably account for much of the disability associated with Huntington's disease. Motor dysfunction, however, including gait and balance disturbances, chorea and dystonia, parkinsonism, and other signs and symptoms (eg, oculomotor abnormalities, dysarthria, and dysphagia), contribute substantially to the functional burden of this disorder. (Source: Lancet Neurology)

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A novel target for Huntington's disease: ERK at the crossroads of signaling

BioEssays — Wed, 16 Nov 2011 05:00:00 +0100

AbstractActivating the ERK pathway (extracellular signal‐regulated kinase pathway) has proven beneficial in several models of Huntington's disease (HD), and drugs that are protective in HD models have recently been found to activate ERK. Thus, the ERK cascade may be a potential target for therapeutic intervention in this currently untreatable disorder. HD is caused by an expanded polyglutamine repeat in the huntingtin (Htt) protein that actuates a diverse set of pathogenic mechanisms. In response to mutant Htt, ERK is activated and directs a protective transcriptional response and inhibits caspase activation. Paradoxically, Htt also interferes with several signaling events of the ERK pathway. Mutant Htt compromises the ERK‐dependent transcriptional response to corticostriatal BDNF sign...

Role of FK506 Binding Proteins in Neurodegenerative Disorders.

Current Medicinal Chemistry — Wed, 16 Nov 2011 05:00:00 +0100

Authors: Chattopadhaya S, Harikishore A, Yoon HS Abstract Protein misfolding has been implicated in the pathophysiology of several neurodegenerative 'amyloidoses' that includes Alzheimer's, Parkinson's, Huntington's disease, frontotemporal dementia and amyotrophic lateral sclerosis. Accumulation of misfolded proteins into ordered fibrillar intra- or extracellular amyloids results in brain lesions that in turn lead to injury and neuronal loss. The appearance of protein aggregates in the diseased brain hints at an inability of cellular chaperones to properly assist folding of client proteins. Not surprisingly, studies involving cell-based and animal models of the neurodegenerative diseases have shown that overexpression of molecular chaperones can provide neuroprotection. Together wi...

Protein misfolding: Tracking a toxic polyQ epitope

Nature Chemical Biology — Tue, 15 Nov 2011 05:00:00 +0100

Nature Chemical Biology 7, 861 (2011). doi:10.1038/nchembio.718 Author: Motomasa Tanaka The monoclonal antibody 3B5H10 that recognizes diffuse mutant huntingtin predicts cell death in primary striatal neurons. Biochemical and biophysical analyses reveal that the 3B5H10 epitope is exposed in a monomeric state, identifying this specific conformation as a toxic agent in Huntington's disease. (Source: Nature Chemical Biology)

Memory deficits in the transgenic rat model of Huntington's disease.

Behavioural Brain Research — Tue, 15 Nov 2011 05:00:00 +0100

In this study we investigated the memory function of the transgenic rat model of Huntington's disease (tgHD) in the object location (OLT) and the object recognition task (ORT). Several studies have shown that the recent developed tgHD rat model resembles the human phenotype of HD. Impairments of spatial and object recognition memory in the OLT and ORT, however, have to our knowledge not yet been reported in this transgenic model. Our findings show that in both early and late stages of the disease the tgHD rats have clear deficits for both visuospatial and visual object memory. Since HD patients are known to be impaired in both types of memory, these results confirm the validity of this tgHD rat as a model for the human HD phenotype. PMID: 22101303 [PubMed - as supplied by publisher] (S...

Neurodegenerative processes in Huntington's disease. - Bano D, Zanetti F, Mende Y, Nicotera P.

SafetyLit: All (Unduplicated) — Sun, 13 Nov 2011 23:51:22 +0100

Huntington's disease (HD) is a complex and severe disorder characterized by the gradual and the progressive loss of neurons, predominantly in the striatum, which leads to the typical motor and cognitive impairments associated with this pathology. HD is cau... (Source: SafetyLit: All (Unduplicated))

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Huntington Hospital expands emergency services

Los Angeles Times - Science — Sun, 13 Nov 2011 05:00:00 +0100

The first phase of the $80-million project at the Pasadena facility is to open in March.Huntington Hospital is more than halfway done with an expansion of its emergency department as it seeks to keep pace with rising demand for emergency room services. (Source: Los Angeles Times - Science)

Application of clustering analyses to the diagnosis of Huntington disease in mice and other diseases with well-defined group boundaries

Computer Methods and Programs in Biomedicine — Fri, 11 Nov 2011 16:39:29 +0100

In this study, we introduced a new method of employing a clustering algorithm to develop a diagnostic model that can differentially diagnose a single unknown subject in a disease with well-defined group boundaries. We used three tests to assess the suitability and the accuracy required for diagnostic purposes of the four clustering algorithms we investigated (K-means, Fuzzy, Hierarchical, and Medoid Partitioning). To accomplish this goal, we studied the striatal metabolomic profile of R6/2 Huntington disease (HD) transgenic mice and that of wild type (WT) mice using high field in vivo proton NMR spectroscopy (9.4T). We tested all four clustering algorithms (1) with the original R6/2 HD mice and WT mice, (2) with unknown mice, whose status had been determined via genotyping, and (3) with th...

Design of experiments to observe radiation stabilized Rayleigh-Taylor instability growth at an embedded decelerating interface

Physics of Plasmas — Fri, 11 Nov 2011 14:56:35 +0100

C. M. Huntington, C. C. Kuranz, R. P. Drake, A. R. Miles, S. T. Prisbrey et al. Using a hohlraum produced thermal x-ray drive at the National Ignition Facility (NIF) to create pressure by material ablation, a shock exceeding 200 Mbar can be driven through a planar, solid-density target and into a lower-density foam material. The shock driven through the foam is strongly radiati ... [Phys. Plasmas 18, 112703 (2011)] published Thu Nov 10, 2011. (Source: Physics of Plasmas)

[Letter] Competencies: A Cure for Pre-Med Curriculum

Science: Current Issue — Fri, 11 Nov 2011 06:40:50 +0100

Authors: Winston A. Anderson,, Richard M. Amasino, Manuel Ares Jr., Utpal Banerjee, Bonnie Bartel, Victor G. Corces, Catherine L. Drennan, Sarah C. R. Elgin, Irving R. Epstein, Ellen Fanning, Louis J. Guillette Jr., Jo Handelsman, Graham F. Hatfull, Ronald Raymond Hoy, Darcy Kelley, Leslie A. Leinwand, Richard Losick, Yi Lu, David G. Lynn, Claudia Neuhauser, Diane K. O'Dowd, Toto Olivera, Pavel Pevzner, Rebecca R. Richards-Kortum, Jasper Rine, Robert L. Sah, Scott A. Strobel, Graham C. Walker, David R. Walt, Isiah M. Warner, Sue Wessler, Huntington F. Willard, Richard N. Zare (Source: Science: Current Issue)

New Drug for Huntington's

Medical Headlines From Ivanhoe.com — Fri, 11 Nov 2011 05:00:00 +0100

(Ivanhoe Newswire) -- No drug has been shown to improve the loss of the ability to move muscles voluntarily, until now. A new drug called pridopidine stabilizes dopamine signaling in areas of the brain that control movement and coordination. (Source: Medical Headlines From Ivanhoe.com)

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Premutation huntingtin allele adopts a non-B conformation and contains a hot spot for DNA damage.

Biochemical and Biophysical Research communications — Fri, 11 Nov 2011 05:00:00 +0100

Authors: Jarem DA, Delaney S Abstract The expansion of a CAG trinucleotide repeat (TNR) sequence has been linked to several neurological disorders, for example, Huntington's disease (HD). Healthy individuals have 5-35 CAG repeats. Those with 36-39 repeats have the premutation allele, which is known to be prone to expansion. In the disease state, greater than 40 repeats are present. Interestingly, the formation of non-B DNA conformations by the TNR sequence is proposed to contribute to the expansion. Here we provide the first structural and thermodynamic analysis of a premutation length TNR sequence. Using chemical probes of nucleobase accessibility, we found that similar to (CAG)(10), the premutation length sequence (CAG)(36) forms a stem-loop hairpin and contains a hot spot for DN...

Behavioral Phenotyping of Mouse Models of Neurodegeneration

Springer protocols feed by Neuroscience — Fri, 11 Nov 2011 05:00:00 +0100

Neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington’s (HD), Parkinson’s (PD) and Alzheimer’s diseases (AD), are characterized by the loss of structure and function of specific neuronal circuitry in the brain. As a result of this loss, behavioral symptoms occur progressively. Understanding the causes of neurodegeneration is fundamental for the development of new therapeutic targets. For this purpose, several animal models of neurodegenerative disorders have been generated and characterized. During the characterization, behavioral science plays a crucial role by identifying specific symptoms in these animal models of human disorders. Later on, it also allows scientists to verify the efficacy of new treatments. This chapter describes some of ...

Imaging Presynaptic Exocytosis in Corticostriatal Slices

Springer protocols feed by Neuroscience — Fri, 11 Nov 2011 05:00:00 +0100

Optical imaging is a valuable tool for investigating alterations in membrane turnover and vesicle trafficking. Established techniques can easily be adapted to study the mechanisms of synaptic dysfunction in models of neuropsychiatric disorders and neurodegenerative diseases, such as drug addiction, Parkinsonism, and Huntington’s disease. Fluorescent endocytic tracers, including FM1-43, have been used to optically monitor synaptic vesicle fusion and measure synaptic function in various preparations, including chromaffin cells, dissociated cell cultures, and brain slices. In this chapter, we describe a technique that provides a direct measure of pathway-specific exocytosis from glutamatergic corticostriatal terminals. (Source: Springer protocols feed by Neuroscience)

Pridopidine Down But Maybe Not Out in Huntington'sPridopidine Down But Maybe Not Out in Huntington's

Medscape Today Headlines — Fri, 11 Nov 2011 01:36:27 +0100

Although it missed the primary endpoint, results of a phase 3 study show pridopidine was well tolerated and seems to have some benefits on motor symptoms in HD; experts agree it merits further study. Medscape Medical News (Source: Medscape Today Headlines)

Huntington's Disease - Pridopidine Shows Promise In Trial

Health News from Medical News Today — Thu, 10 Nov 2011 13:00:00 +0100

According to results of the phase 3 MermaiHD trial published Online First in The Lancet Neurology, a unique drug (pridopidine) that stabilizes dopamine signaling in areas of the brain controlling movement and coordination in patients with Huntington's disease (HD), a condition characterized by an imbalance in the signaling chemical dopamine, seems to be well tolerated and merits further investigation. So far, no medication has demonstrated the ability to improve the loss of the ability to move muscles voluntarily... (Source: Health News from Medical News Today)

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Reliability of immunolabelling in the determination of Huntington's disease neuropathy

Brain — Wed, 09 Nov 2011 05:00:00 +0100

(Source: Brain)

Reply: Reliability of immunolabelling in the determination of Huntington's disease neuropathy

Brain — Wed, 09 Nov 2011 05:00:00 +0100

(Source: Brain)

Inhibition of spinal cord dorsal horn neuronal activity by electrical stimulation of the cerebellar cortex

Journal of Neurophysiology — Wed, 09 Nov 2011 05:00:00 +0100

This study provided the first evidence to support this hypothesis. Thirty-one wide-dynamic-range neurons from the left lumbar and 27 from the right lumbar spinal dorsal horn were recorded in response to graded mechanical stimulation (brush, pressure, and pinch) at the hind paws. Electrical stimulation of the cerebellar cortex of the left intermediate hemisphere significantly reduced spinal cord dorsal horn neuron-evoked responses bilaterally in response to peripheral high-intensity mechanical stimuli. It is concluded that the cerebellum may play a potential antinociceptive role, probably through activating descending inhibitory pathways indirectly. (Source: Journal of Neurophysiology)

Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres

European Journal of Human Genetics — Wed, 09 Nov 2011 05:00:00 +0100

Authors: Maartje C Van Rij, Marjan De Rademaeker, Céline Moutou, Jos CFM Dreesen, Martine De Rycke, Inge Liebaers, Joep PM Geraedts, Christine EM De Die-Smulders & Stéphane Viville (Source: European Journal of Human Genetics)

Five choice serial reaction time performance in the Hdh(Q92) mouse model of Huntington's disease.

Brain Research Bulletin — Wed, 09 Nov 2011 05:00:00 +0100

This study indicates that the Hdh(Q92/Q92) mice may have deficits in aspects of attentional function, in particular disruption in the ability to maintain attention in the visuospatial domain, suggesting that this knock-in mouse model of Huntington's disease may be a relevant model of the disease for the testing of novel therapeutic interventions. PMID: 22085744 [PubMed - as supplied by publisher] (Source: Brain Research Bulletin)

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Drug Disappoints for Huntington's Tx (CME/CE)

MedPage Today Neurology — Tue, 08 Nov 2011 14:30:00 +0100

(MedPage Today) -- The dopaminergic stabilizer pridopidine (Huntexil) did not prove effective in the treatment of Huntington's disease, according to results from a Phase III randomized trial. (Source: MedPage Today Neurology)

New Study Uncovers How Brain Cells Degrade Dangerous Protein Aggregates

Health News from Medical News Today — Tue, 08 Nov 2011 08:00:00 +0100

Researchers at the RIKEN Brain Science Institute (BSI) have discovered a key mechanism responsible for selectively degrading aggregates of ubiquitinated proteins from the cell. Their findings indicate that the capture and removal of such aggregates is mediated by the phosphorylation of a protein called p62, opening the door to new avenues for treating neurodegenerative diseases such as Huntington's disease and Alzheimer's disease... (Source: Health News from Medical News Today)

Horizon scanning: Phase III study of pridopidine in the treatment of Huntington's disease

NeLM - News — Tue, 08 Nov 2011 05:00:00 +0100

Source: Lancet Neurology Area: News The authors note that Huntington's disease has an estimated prevalence of around 5-7 per 100,000; recent reports suggest that actual figures may be at least double this figure. This progressive, neurodegenerative disease is associated with a range of cognitive, behavioural and motor deficits that substantially affect patient's daily functioning, ultimately leading to loss of independence and premature death. No firm conclusions can be drawn on the best treatments to use to control motor and non-motor symptoms of the disease. Although tetrabenazine is effective for the control of chorea, it is associated with serious adverse events; antipsychotics are used widely off-label for this and for some behavioural problems. ...

New study uncovers how brain cells degrade dangerous protein aggregates

EurekAlert! - Medicine and Health — Mon, 07 Nov 2011 05:00:00 +0100

(RIKEN) Researchers at the RIKEN Brain Science Institute have discovered a key mechanism responsible for selectively degrading aggregates of ubiquitinated proteins from the cell. Their findings indicate that the capture and removal of such aggregates is mediated by the phosphorylation of a protein called p62, opening the door to new avenues for treating neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. (Source: EurekAlert! - Medicine and Health)

'I put it on the back burner most days': Living with chronic risk

Health: — Mon, 07 Nov 2011 05:00:00 +0100

This article adopts a ‘chronic risk’ perspective to explore living at risk of Huntington disease (HD), a fatal genetic disorder. Qualitative data analysis suggested two broad themes that illustrated living with chronic risk: (1) biographical disruption, including threats to self-identity and changes to relationships with others; and (2) zones of relevance, the conditions under which risk is or is not salient. Findings are relevant to the provision of genetics health services, particularly in follow-up support to individuals at risk for HD and their families. (Source: Health:)

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Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY

Journal of Neurology, Neurosurgery and Psychiatry — Mon, 07 Nov 2011 05:00:00 +0100

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene. HD usually manifests in adult life, causing motor impairments, cognitive decline and behavioural/psychiatric alterations. HD is devastating and inevitably fatal; currently, no disease modifying treatment is established.1 Historically, the study of HD has benefited strikingly from multicentre research initiatives, typified by the international collaborative effort that identified the causative CAG repeat expansion in the HTT gene in 1993.2 Much effort at present is focused on identifying therapeutic targets and developing treatments that may delay onset of the disease, or slow down or stop the progression of HD once it manifests. With a prevalence of 5–8/100 ...

Pathophysiological Modeling of Obsessive-Compulsive Disorder: Challenges, and Progress

Biological Psychiatry — Sat, 05 Nov 2011 23:13:35 +0100

Animal models of disease can enormously advance our understanding of pathophysiology and the development of new treatments. Insight into Parkinson's disease, for example, has been greatly advanced by the demonstration that recapitulating pathologic degeneration of substantia nigra dopaminergic neurons produces behavioral changes reminiscent of the disorder and by subsequent pathophysiologic and therapeutic investigations in this model (). Genetic models of Alzheimer's and Huntington's diseases have likewise been enormously fruitful in shining light on the pathophysiology of these conditions and identifying new therapeutic targets (). Modeling of most psychiatric conditions has proven much more difficult, which has retarded the development of novel, pathophysiologically informed therapeutic...

Cortical metabolites as biomarkers in the R6/2 model of Huntington's disease

Journal of Cerebral Blood Flow — Wed, 02 Nov 2011 04:00:00 +0100

Cortical metabolites as biomarkers in the R6/2 model of Huntington's disease Journal of Cerebral Blood Flow & Metabolism advance online publication, November 2, 2011. doi:10.1038/jcbfm.2011.157 Authors: Lori Zacharoff, Ivan Tkac, Qingfeng Song, Chuanning Tang, Patrick J Bolan, Silvia Mangia, Pierre-Gilles Henry, Tongbin Li & Janet M Dubinsky (Source: Journal of Cerebral Blood Flow)

Protein Form Linked To Huntington's Disease Identified By Gladstone Scientists

Health News from Medical News Today — Tue, 01 Nov 2011 07:00:00 +0100

Scientists at the Gladstone Institutes have discovered how a form of the protein linked to Huntington's disease influences the timing and severity of its symptoms, offering new avenues for treating not only this disease, but also a variety of similar conditions. In a paper published in Nature Chemical Biology, the laboratory of Gladstone Senior Investigator Steven Finkbeiner, MD, PhD, singles out one form of a misfolded protein in neurons that best predicts whether the neuron will die... (Source: Health News from Medical News Today)

Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 01 Nov 2011 04:00:00 +0100

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with pho...

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Huntington's Biomarker Discovery Could Set Tone for Trials

Clinical Neurology News — Tue, 01 Nov 2011 04:00:00 +0100

A biomarker found in the blood of patients with Huntington's disease appears to mark early stages of the disease and measure response to treatment, without confusing signs of Huntington's with those of other neurodegenerative diseases. (Source: Clinical Neurology News)

CAG repeat size in the normal HTT allele and age of onset in Huntington's disease

Movement Disorders — Tue, 01 Nov 2011 04:00:00 +0100

(Source: Movement Disorders)

Increased 90-kDa ribosomal S6 kinase (Rsk) activity is protective against mutant huntingtin toxicity

Molecular Neurodegeneration — Mon, 31 Oct 2011 04:00:00 +0100

Conclusion: The increase of Rsk levels and activity would act as a compensatory mechanism with capacity to prevent mhtt-mediated cell death. We propose Rsk as a good target for neuroprotective therapies in HD. (Source: Molecular Neurodegeneration)

Gladstone scientists identify protein form linked to Huntington's disease

EurekAlert! - Medicine and Health — Sun, 30 Oct 2011 04:00:00 +0100

(Gladstone Institutes) Scientists at the Gladstone Institutes have discovered how a form of the protein linked to Huntington's disease influences the timing and severity of its symptoms, offering new avenues for treating not only this disease, but also a variety of similar conditions. (Source: EurekAlert! - Medicine and Health)

In vitro repair of DNA hairpins containing various numbers of CAG/CTG trinucleotide repeats.

DNA Repair — Sat, 29 Oct 2011 04:00:00 +0100

Authors: Zhang T, Huang J, Gu L, Li GM Abstract Expansion of CAG/CTG trinucleotide repeats (TNRs) in humans is associated with a number of neurological and neurodegenerative disorders including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism leads to TNR instability. However, the molecular mechanism by which cells recognize and repair CAG/CTG hairpins is largely unknown. Recent studies have identified a novel DNA repair pathway specifically removing (CAG)(n)/(CTG)(n) hairpins, which is considered a major mechanism responsible for TNR instability. The hairpin repair (HPR) system targets the repeat tracts for incisions in the nicked strand in an error-free manner. To determine the substrate spectru...

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Serum levels of N‐acetylaspartate in Huntington's disease: Preliminary results

Movement Disorders — Fri, 28 Oct 2011 04:00:00 +0100

(Source: Movement Disorders)

Sirtuins in Neurodegenerative Diseases: A Biological-Chemical Perspective.

Neuro-Degenerative Diseases — Fri, 28 Oct 2011 04:00:00 +0100

Authors: Raghavan A, Shah ZA Abstract Sirtuins, commonly known as NAD(+)-dependent class III histone deacetylase enzymes, have been extensively studied to evaluate their potential role in different disease states. Based on the published literature, sirtuins have been implicated in providing a myriad of intrinsic and extrinsic biological effects, which in turn may play an important role in the treatment of various disorders such as type II diabetes, obesity, cancer, aging and different neurodegenerative diseases. In particular, a number of studies have unequivocally supported the idea of sirtuins having therapeutic potential in neurodegenerative diseases such as stroke, ischemic brain injury, Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral scle...

GPE and GPE analogues as promising neuroprotective agents.

Mini Reviews in Medicinal Chemistry — Fri, 28 Oct 2011 04:00:00 +0100

Authors: Cacciatore I, Cornacchia C, Baldassarre L, Fornasari E, Mollica A, Stefanucci A, Pinnen F Abstract The tripeptide glycine-proline-glutamate (GPE) is the naturally cleaved N-terminal tripeptide of insulin-like growth factor-1 (IGF-1) in brain tissues by an acid protease. Although GPE does not bind to IGF-1 receptors and its mode of action is not clear, in vitro studies have demonstrated its ability to stimulate acetylcholine and dopamine release, as well as to protect neurones from diverse induced brain injures. More importantly, GPE has been shown to have potent neuroprotective effects in numerous animal models of hypoxic-ischemic brain injury and neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's diseases. As a consequence, GPE was suggested to b...

The Seeds of Neurodegeneration: Prion-like Spreading in ALS

Cell — Fri, 28 Oct 2011 00:00:00 +0100

Magdalini Polymenidou, Don W. Cleveland. Misfolded proteins accumulating in several neurodegenerative diseases (including Alzheimer, Parkinson, and Huntington diseases) can cause aggregation of their native counterparts through a mechani.... (Source: Cell)