MedWorm: ALS

Researchers Find Additional Benefits Of Cord Blood Cells In Mice Modeling ALS

Health News from Medical News Today — Tue, 07 Feb 2012 09:00:00 +0100

Repeated, low-dose injections of mononuclear cells derived from human umbilical cord blood (MNC hUCB, tradename: U-CORD-CELL™) have been found effective in protecting motor neuron cells, delaying disease progression and increasing lifespan for mice modeling amyotrophic lateral sclerosis, or ALS, also referred to as Lou Gehrig's disease, report University of South Florida researchers and colleagues from Saneron CCEL Therapeutics, Inc., and the Ribeirao Preto School of Medicine at the University of Sao Paulo, Brazil. Their study was published online in the journal PLoS ONE... (Source: Health News from Medical News Today)

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A Patient With ALS and Atypical Clinical FeaturesA Patient With ALS and Atypical Clinical Features

Medscape Today Headlines — Mon, 06 Feb 2012 04:00:00 +0100

The presentation of amyotrophic lateral sclerosis can be variable, and proper diagnosis is essential for prognosis and management. In this case, symptoms were atypical, and diagnosis came too late. Journal of Medical Case Reports (Source: Medscape Today Headlines)

USF and Saneron researchers find additional benefits of cord blood cells in mice modeling ALS

EurekAlert! - Medicine and Health — Fri, 03 Feb 2012 05:00:00 +0100

(University of South Florida (USF Health)) Repeated, low-dose injections of mononuclear cells derived from human umbilical cord blood were effective in protecting motor neuron cells, delaying disease progression and increasing lifespan for mice modeling amyotrophic lateral sclerosis, or ALS, also referred to as Lou Gehrig's disease. The findings are reported in the online journal PLoS ONE. (Source: EurekAlert! - Medicine and Health)

8-OHQs Rescue Diverse Proteotoxicity Models in Distinct Ways [Protein Structure and Folding]

Journal of Biological Chemistry — Fri, 03 Feb 2012 05:00:00 +0100

No current therapies target the underlying cellular pathologies of age-related neurodegenerative diseases. Model organisms provide a platform for discovering compounds that protect against the toxic, misfolded proteins that initiate these diseases. One such protein, TDP-43, is implicated in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. In yeast, TDP-43 expression is toxic, and genetic modifiers first discovered in yeast have proven to modulate TDP-43 toxicity in both neurons and humans. Here, we describe a phenotypic screen for small molecules that reverse TDP-43 toxicity in yeast. One group of hit compounds was 8-hydroxyquinolines (8-OHQ), a class of clinically relevant bioactive metal chelators related to clioquinol. S...

Iron homeostasis in astrocytes and microglia is differentially regulated by TNF‐α and TGF‐β1

Glia — Fri, 03 Feb 2012 01:14:23 +0100

AbstractAbnormal iron homeostasis is increasingly thought to contribute to the pathogenesis of several neurodegenerative disorders. We have previously reported impaired iron homeostasis in a mouse model of spinal cord injury and in a mouse model of amyotrophic lateral sclerosis. Both these disorders are associated with CNS inflammation. However, what effect inflammation, and in particular, inflammatory cytokines have on iron homeostasis in CNS glia remains largely unknown. Here we report that the proinflammatory cytokine TNF‐α, and the anti‐inflammatory cytokine TGF‐β1 affect iron homeostasis in astrocytes and microglia in distinct ways. Treatment of astrocytes in vitro with TNF‐α induced the expression of the iron importer “divalent iron transporter 1” (DMT1) and suppressed...

Dr. Richard K. Olney, A.L.S. Researcher, Dies at 64.

NYT Health — Thu, 02 Feb 2012 23:13:10 +0100

Dr. Olney, a leading researcher of A.L.S., commonly known as Lou Gehrig’s disease, dies eight years after learning that he himself had it. (Source: NYT Health)

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Concussion Is a Serious Problem for Child Athletes

Scientific American - Official RSS Feed — Wed, 01 Feb 2012 13:00:00 +0100

The dangers of life in the National Football League made headlines in 2009, when a study commissioned by the NFL found that retired players were 19 times more likely than other men of similar ages to develop severe memory problems. The obvious culprit: continued play after repeated head injuries. Indeed, head injury can imitate many types of neurodegenerative disease, including Parkinson’s disease and, as journalist Jeffrey Bartholet reports in “The Collision Syndrome,” on page 66, perhaps even amyotrophic lateral sclerosis, commonly referred to as Lou Gehrig’s disease. [More] (Source: Scientific American - Official RSS Feed)

Withdrawal of Invasive Home Mechanical Ventilation in Patients with Advanced Amyotrophic Lateral Sclerosis: Ten Years of Danish Experience

Journal of Palliative Medicine — Sat, 28 Jan 2012 04:13:01 +0100

Journal of Palliative Medicine , Vol. 0, No. 0. (Source: Journal of Palliative Medicine)

Certain Brain Cells Become Toxic in Lou Gehrig's Disease

Scientific American - Official RSS Feed — Wed, 25 Jan 2012 14:00:00 +0100

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neuromuscular disease that affects about 130,000 people worldwide a year. The vast majority of patients are isolated cases with no known family history of the disease. They usually start developing symptoms of the loss of motor neurons in middle age and die within five years of diagnosis. Researchers know very little about what causes ALS. Now a recent study in Nature Biotechnology suggests that the neuron death associated with the disease may be caused by astrocytes, a type of brain cell that normally helps neurons. [More] (Source: Scientific American - Official RSS Feed)

Homozygous SMN2 deletion is a protective factor in the Swedish ALS populations

European Journal of Human Genetics — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Philippe Corcia, Caroline Ingre, Helene Blasco, Rayomand Press, Julien Praline, Catherine Antar, Charlotte Veyrat-Durebex, Yves-Olivier Guettard, William Camu, Peter M Andersen, Patrick Vourc'h & Christian R Andres (Source: European Journal of Human Genetics)

Mandibuloptosis as a cause of supine choking in a patient with amyotrophic lateral sclerosis

Journal of Neurology — Tue, 24 Jan 2012 18:09:45 +0100

Content Type Journal ArticleCategory Letter to the EditorsPages 1-2DOI 10.1007/s00415-012-6416-7Authors Michito Namekawa, Department of Neurology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, JapanHiroto Ito, Department of Oral and Maxillofacial Surgery, Jichi Medical University, Tochigi, JapanTomoaki Kameda, Department of Neurology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, JapanImaharu Nakano, Department of Neurology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan Journal Journal of NeurologyOnline ISSN 1432-1459Print ISSN 0340-5354 (Source: Journal of Neurology)

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Concurrent multiple sclerosis and amyotrophic lateral sclerosis: where inflammation and neurodegeneration meet?

Journal of Neuroinflammation — Tue, 24 Jan 2012 05:00:00 +0100

The concurrence of multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) is exceedingly rare and the pathological features have not been examined extensively. Here we describe the key pathological features of a 40 year old man with pathologically confirmed concurrent MS and ALS.This is the most pathologically illustrative case of coincident MS and ALS demonstrating inflammatory and neurodegenerative features characteristic of each disease, and is the first to exhibit the presence of TDP-43 inclusions in this clinical entity. The intricate relationship between neuroinflammation and neurodegeneration in these diseases is discussed. (Source: Journal of Neuroinflammation)

Diffusion Tensor Imaging of Basal Ganglia and Thalamus in Amyotrophic Lateral Sclerosis

Journal of Neuroimaging — Tue, 24 Jan 2012 05:00:00 +0100

CONCLUSIONSThe increased MD in basal ganglia and thalamus and decreased FA in globus pallidus and thalamus are indicative of neuronal loss or dysfunction in these structures. J Neuroimaging 2012;XX:1–7. (Source: Journal of Neuroimaging)

Towards Unveiling the Genetics of Neurodegenerative Diseases

Seminars in Neurology — Sat, 21 Jan 2012 05:00:00 +0100

Semin Neurol 2011; 31: 531-541DOI: 10.1055/s-0031-1299791ABSTRACTIn addition to sharing several clinical, pathologic, and molecular characteristics, many neurodegenerative disorders show extensive familial histories suggesting a substantial contribution of genetic factors to disease causation and progression. In this review, the authors provide overviews of the status of current genetics research in Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Across these four disorders alone, nearly 60 different loci can now be considered as established to be involved in pathogenesis for both Mendelian and non-Mendelian disease forms. In addition to reviewing the most compelling of these loci based on current data from genome-wide association studi...

Inhibition of Amyloid Precursor Protein Beta-Secretase Cleavage Site Affects Survival and Motor Functions of Amyotrophic Lateral Sclerosis Transgenic Mice.

Neuro-Degenerative Diseases — Sat, 21 Jan 2012 05:00:00 +0100

Conclusion: APP cleavage products might contribute to the degeneration in ALS, and early inhibition of the APP process may ameliorate disease progression. PMID: 22269310 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)

[Errata] Erratum

Lancet Neurology — Sat, 21 Jan 2012 01:16:38 +0100

Gijselinck I, Van Langenhove T, van der Zee J, et al. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol 2012; 11: 54–65—In this Article (published online Dec 8) the citation at the top of the margin on the first page should have read Lancet Neurol2012; 11: 54–65. This correction has been made to the online version as of December 22, 2011. (Source: Lancet Neurology)

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Inhibition of Amyloid Precursor Protein Beta-Secretase Cleavage Site Affects Survival and Motor Functions of Amyotrophic Lateral Sclerosis Transgenic Mice

Neurodegenerative Diseases — Fri, 20 Jan 2012 23:00:00 +0100

Neurodegenerative Dis (DOI:10.1159/000334774) (Source: Neurodegenerative Diseases)

Movement In Animals With Amyotrophic Lateral Sclerosis Improved By Blocking Metabolic Protein

Health News from Medical News Today — Thu, 19 Jan 2012 08:00:00 +0100

Turning off a protein that helps cells balance energy increases animal mobility and reduces the death of nerve cells that control movement in animal models of amyotrophic lateral sclerosis (ALS), according to a study in The Journal of Neuroscience. The findings may one day guide new directions for the treatment of the progressive neurodegenerative disorder, for which there is currently no cure. ALS is characterized by the breakdown of brain and spinal cord nerve cells that control muscles, eventually leading to weakness and death... (Source: Health News from Medical News Today)

The role of kynurenines in the pathomechanism of amyotrophic lateral sclerosis and multiple sclerosis: therapeutic implications

Journal of Neural Transmission — Thu, 19 Jan 2012 06:58:54 +0100

Abstract Tryptophan is one of the essential amino acids, 80% of which is catabolised in the extrahepatic tissues by indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme of the kynurenine pathway. Metabolites along the kynurenine pathway have been implicated to play a role in the pathomechanism of neuroinflammatory and neurodegenerative disorders. Changes in the concentration levels of kynurenines can shift the balance to pathological conditions. The ability to influence the metabolism towards the neuroprotective branch of the kynurenine pathway, i.e. towards kynurenic acid (KYNA) synthesis, may be one option in preventing neurodegenerative diseases. Three potential therapeutic strategies could be feasible to develop drugs to live up to expectations: (1) chemically r...

Improving survival in a large French ALS center cohort

Journal of Neurology — Thu, 19 Jan 2012 06:51:46 +0100

Abstract The aim of this work was to determine whether survival changed during 2002–2009 at a French amyotrophic lateral sclerosis (ALS) center. We included all patients with ALS who were seen consecutively at the center from January 2002–May 2009. Participants were followed from date of first visit through death, date of censoring, or December 31, 2009, whichever occurred first. Cox proportional hazard models computed hazard ratios (HR; 95% confidence interval CI) of death, and flexible modeling of continuous predictors (splines) assessed trends in survival. We analyzed a total of 2,037 ALS patients, of whom 1,471 died before the end of follow-up. Median survival was 2.83 years from onset and 1.65 years from first visit. Compared to patients first seen befor...

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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Decreased heart rate variability predicts death in amyotrophic lateral sclerosis

Muscle and Nerve — Wed, 18 Jan 2012 14:53:35 +0100

Conclusion –Low HR CV is a potential marker of prognosis in ALS. (Source: Muscle and Nerve)

Secreted VAPB/ALS8 Major Sperm Protein Domains Modulate Mitochondrial Localization and Morphology via Growth Cone Guidance Receptors.

Developmental Cell — Wed, 18 Jan 2012 05:00:00 +0100

Authors: Han SM, Tsuda H, Yang Y, Vibbert J, Cottee P, Lee SJ, Winek J, Haueter C, Bellen HJ, Miller MA Abstract The VAPB/ALS8 major sperm protein domain (vMSP) is implicated in amyotrophic lateral sclerosis and spinal muscular atrophy, yet its function in the nervous system is not well understood. In Caenorhabditis elegans and Drosophila, the vMSP is cleaved from its transmembrane anchor and secreted in a cell type-specific fashion. We show that vMSPs secreted by neurons act on Lar-like protein-tyrosine phosphatase and Roundabout growth cone guidance receptors expressed in striated muscle. This signaling pathway promotes Arp2/3-dependent actin remodeling and mitochondrial localization to actin-rich muscle I-bands. C. elegans VAPB mutants have mitochondrial localization, morphol...

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 ...

Sleep-Disordered Breathing in Neurodegenerative Diseases

Current Neurology and Neuroscience Reports — Tue, 17 Jan 2012 07:06:32 +0100

Abstract Sleep disorders are common in neurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), hereditary ataxias, and Alzheimer’s disease (AD). Type, frequency, and severity of sleep disturbances vary depending on each of these diseases. Cell loss of the brainstem nuclei that modulates respiration, and dysfunction of bulbar and diaphragmatic muscles increase the risk for sleep-disordered breathing (SDB) in MSA and ALS. The most relevant SDB in MSA is stridor, whereas in ALS nocturnal hypoventilation due to diaphragmatic weakness is the most common sleep breathing abnormality. Stridor and nocturnal hypoventilation are associated with reduced survival in MSA and ALS. In contrast, sleep apnea seems ...

Blocking metabolic protein improves movement in animals with ALS

EurekAlert! - Social and Behavioral Science — Tue, 17 Jan 2012 05:00:00 +0100

(Society for Neuroscience) Turning off a protein that helps cells balance energy increases animal mobility and reduces the death of nerve cells that control movement in animal models of amyotrophic lateral sclerosis (ALS), according to a study in the Jan. 18 issue of the Journal of Neuroscience. The findings may one day guide new directions for the treatment of the progressive neurodegenerative disorder, for which there is currently no cure. (Source: EurekAlert! - Social and Behavioral Science)

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Regional spread pattern predicts survival in patients with sporadic amyotrophic lateral sclerosis

European Journal of Neurology — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions: We have provided evidence that not all spread in ALS is contiguous and that the nature of symptom progression influences survival. Patients with sALS with ‘interposed patterns’ had a worse prognosis, whereas patients with caudo‐rostral pattern fared better than the rest. (Source: European Journal of Neurology)

Altered RNA metabolism and amyotrophic lateral sclerosis

Annals of Indian Academy of Neurology — Tue, 17 Jan 2012 05:00:00 +0100

This article reviews the current direction of research efforts toward understanding the role of RNA (ribonucleic acid) processing regulation in ALS and possible therapeutic pathways in this fatal disease. (Source: Annals of Indian Academy of Neurology)

Teaching NeuroImages: Somatic muscle fasciculations detected by electrocardiography

Neurology — Mon, 16 Jan 2012 05:00:00 +0100

(Source: Neurology)

Impaired expression of insulin‐like growth factor‐1 system in skeletal muscle of amyotrophic lateral sclerosis patients

Muscle and Nerve — Sun, 15 Jan 2012 03:11:48 +0100

Conclusion:In this study we describe the abnormal expression of the IGF‐1 system in skeletal muscle of sALS patients that could participate in motor neuron degeneration and should be taken into account when developing treatments with IGF‐1. Muscle Nerve, 2012 (Source: Muscle and Nerve)

Fasciculation potentials in amyotrophic lateral sclerosis and the diagnostic yield of the Awaji algorithm

Muscle and Nerve — Sun, 15 Jan 2012 03:11:43 +0100

Conclusion: The sensitivity of the Awaji algorithm is lower than that of the R‐EEC. Muscle Nerve, 2012 (Source: Muscle and Nerve)

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UBQLN2/P62 cellular recycling pathways in amyotrophic lateral sclerosis and frontotemporal dementia

Muscle and Nerve — Sun, 15 Jan 2012 03:11:39 +0100

AbstractRecent findings highlight a pathologic and functional convergence in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS‐FTD) at the level of protein recycling and disposal. Genes linked to rare cases of familial ALS and ALS‐FTD, like UBQLN2, OPTN, SQSTM1/p62, and VCP, may converge onto a unifying pathogenic pathway and thereby provide novel therapeutic targets common to a spectrum of etiologically diverse forms of ALS and ALS‐FTD. Interactions between these genes need to be further explored to understand their common molecular pathways. Future efforts should be directed toward generation and characterization of in vivo models to dissect the pathogenic mechanisms of ALS and ALS‐FTD and the role of protein degradation pathw...

Screening of the SOD1, FUS, TARDBP, ANG, and OPTN mutations in Korean patients with familial and sporadic ALS.

Neurobiology of Aging — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Kwon MJ, Baek W, Ki CS, Kim HY, Koh SH, Kim JW, Kim SH Abstract About 5% of amyotrophic lateral sclerosis (ALS) cases are known to be familial (fALS) and mutations in SOD1 and other genes are found in more than 20% of fALS patients and in 2%-4% of apparently sporadic ALS (sALS) cases. However, there are few reports on the proportion of fALS and the frequency of mutations in Korean patients with ALS. We screened mutations in the SOD1, FUS, TARDBP, ANG, and OPTN genes in 258 consecutively enrolled Korean patients with ALS from October 2006 to November 2010. The frequency of fALS was estimated to be 3.5% (9/258), and mutations were identified in 88.9% (8/9) of fALS patients but only in 2.8% (7/249) of sALS patients. Seven fALS and 3 sALS patients had mutations in SOD1 gene wh...

Cognitive Impairment in Amyotrophic Lateral SclerosisCognitive Impairment in Amyotrophic Lateral Sclerosis

Medscape Today Headlines — Fri, 13 Jan 2012 04:00:00 +0100

This study examined the prevalence, clinical characteristics, and natural history of cognitive impairment in patients with amyotrophic lateral sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry (Source: Medscape Today Headlines)

Comparison of a row-column speller vs. a novel lateral single-character speller: Assessment of BCI for severe motor disabled patients.

Clinical Neurophysiology — Thu, 12 Jan 2012 05:00:00 +0100

CONCLUSIONS: The results suggest that LSC is an effective alternative to RC, and that LSC still has a margin for potential improvement in bit rate and accuracy. SIGNIFICANCE: The high bit rates and accuracy of LSC are a step forward for the effective use of BCI in clinical applications. PMID: 22244868 [PubMed - as supplied by publisher] (Source: Clinical Neurophysiology)

Muscle ultrasonography: A diagnostic tool for amyotrophic lateral sclerosis.

Clinical Neurophysiology — Thu, 12 Jan 2012 05:00:00 +0100

CONCLUSIONS: Muscle ultrasound can differentiate between amyotrophic lateral sclerosis and mimics with high sensitivity and specificity, and is a sensitive tool to screen for regional lower motor neuron involvement. SIGNIFICANCE: Muscle ultrasonography is a promising tool in the diagnostic work up of ALS. PMID: 22244867 [PubMed - as supplied by publisher] (Source: Clinical Neurophysiology)

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Online use of error-related potentials in healthy users and people with severe motor impairment increases performance of a P300-BCI.

Clinical Neurophysiology — Wed, 11 Jan 2012 05:00:00 +0100

CONCLUSIONS: Error-related potentials as a secondary source of information can be used to increase overall bit rate in a P3 BCI. SIGNIFICANCE: The method should be made available to any patient using the P3 BCI for communication. PMID: 22244309 [PubMed - as supplied by publisher] (Source: Clinical Neurophysiology)

VapB as a regulator of osteoclastogenesis via modulation of PLCγ2-Ca2+-NFAT signaling

FEBS Letters — Wed, 11 Jan 2012 05:00:00 +0100

Highlights: ► We investigate the role of VapB in RANKL-induced osteoclast differentiation. ► Knock-down of VapB suppressed osteoclastogenesis. ► Over-expression of VapB accelerated RANKL-mediated osteoclast differentiation by induction of NFATc1. ► VapB regulates RANKL-mediated osteoclastogenesis via PLCγ2-Ca2+-NFAT signaling.Abstract: VapB has been shown to regulate calcium homeostasis in amyotrophic lateral sclerosis. Calcium signaling is also important in metabolic bone diseases, but the role of VapB in the generation of osteoclasts for bone resorption during osteoclastogenesis is not known. Therefore, we investigated the role of VapB in RANKL-induced osteoclast differentiation. Interestingly, VapB is induced during osteoclastogenesis, and regulates osteoclast differentiation b...

Familial Versus Sporadic Amyotrophic Lateral SclerosisFamilial Versus Sporadic Amyotrophic Lateral Sclerosis

Medscape Today Headlines — Wed, 11 Jan 2012 04:00:00 +0100

With recent landmark studies in the genetics of amyotrophic lateral sclerosis, familial and sporadic ALS, once thought to be separate variants, are now recognized as having common determinants. Brain (Source: Medscape Today Headlines)

Association of amyotrophic lateral sclerosis and Behcet’s disease: is there a relationship? A multi-national case series

Clinical Rheumatology — Tue, 10 Jan 2012 17:00:11 +0100

Abstract Neurological involvement may be seen in 5–30% of the patients with Behcet’s disease (BD). Occasionally, parenchymal neurological involvement in BD can present as a spinal cord syndrome. However, motor neuron disease-like presentation is extremely uncommon. Here we are reporting five patients (all male; median age, 38) fulfilling both International Study Group criteria for BD and El Escorial criteria for amyotrophic lateral sclerosis (ALS). These patients were identified by a questionnaire sent to the members of the Neuro-Behcet Study Group of the International Study Group for BD. Three out of five patients had only motor presentations. In two patients, sensory and urinary manifestations were present as well. Spinal cord MRIs were normal in all, and brain MRIs ...

Ultrasound-Induced Blood-Brain Barrier Opening.

Current Pharmaceutical Biotechnology — Tue, 10 Jan 2012 15:32:58 +0100

Authors: Konofagou EE, Tung YS, Choi J, Deffieux T, Baseri B, Vlachos F Abstract Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS). Worldwide, these four diseases account for more than 20 million patients. In addition, aging greatly increases the risk of neurodegenerative disease. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of the 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. On the other hand, safe ...

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Temporal trend of amyotrophic lateral sclerosis incidence in southern Europe: a population study in the health district of Ferrara, Italy

Journal of Neurology — Tue, 10 Jan 2012 06:48:23 +0100

Abstract Data about the temporal trend of amyotrophic lateral sclerosis (ALS) incidence in southern Europe are scarce. Incidence studies on ALS have been carried out in the health district of Ferrara, Italy, since 1960s. We expanded the previous studies from 1964 to 2009. The study was prospective with a subsequent retrospective intensive survey of multiple sources of case ascertainment. All patients with a definite and probable ALS according to the original El Escorial criteria were selected. There were 130 incident cases in the years 1964–2009 giving an average annual crude incidence of 1.82 per 100,000 population (95% CI 1.53–2.17). An incidence increase during the study period was estimated in women (χ2 test for trend = 7.19, p < 0.01) and in...

d-Amino acid oxidase controls motoneuron degeneration through d-serine [Neuroscience]

Proceedings of the National Academy of Sciences — Tue, 10 Jan 2012 05:00:00 +0100

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving an extensive loss of motoneurons. Aberrant excitability of motoneurons has been implicated in the pathogenesis of selective motoneuronal death in ALS. d-Serine, an endogenous coagonist of N-methyl-d-aspartate receptors, exacerbates motoneuronal death and is increased both in patients with sporadic/familial ALS and in a G93A-SOD1 mouse model of ALS (mSOD1 mouse). More recently, a unique mutation in the d-amino acid oxidase (DAO) gene, encoding a d-serine degrading enzyme, was reported to be associated with classical familial ALS. However, whether DAO affects the motoneuronal phenotype and d-serine increase in ALS remains uncertain. Here, we show that genetic inactivation of DAO in mice reduces the number and...

CAG repeat length in androgen receptor gene is not associated with amyotrophic lateral sclerosis

European Journal of Neurology — Tue, 10 Jan 2012 05:00:00 +0100

Conclusions: Our findings do not support a role of the AR CAG repeat length in ALS. (Source: European Journal of Neurology)

Fatigue, sleep, and nocturnal complaints in patients with amyotrophic lateral sclerosis

European Journal of Neurology — Tue, 10 Jan 2012 05:00:00 +0100

Conclusion: In this study, we demonstrated that fatigue, a troublesome and disabling symptom in ALS, is associated with physical impairment and night‐time complaints (such as nocturia and muscle cramps), suggesting that treating sleep problems might be useful in alleviating fatigue in these patients. (Source: European Journal of Neurology)

Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies.

Neurotoxicology — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Fox DA, Grandjean P, de Groot D, Paule MG Abstract To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period and the development of metabolic-related diseases and neurotoxicity later in life. The four speakers at this symposium presented their research results on different neurotoxic chemicals relating to the developmental origins of health and adult disease (DOHaD). Philippe Grandjean presented epidemiological data on children exposed to inorganic mercury and methylmercury, and discussed the behavioral outcome measures as they relate to age and s...

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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)

Unsolicited Written Narratives as a Methodological Genre in Terminal Illness: Challenges and Limitations

Qualitative Health Research — Mon, 09 Jan 2012 05:00:00 +0100

Stories about illness have proven invaluable in helping health professionals understand illness experiences. Such narratives have traditionally been solicited by researchers through interviews and the collection of personal writings, including diaries. These approaches are, however, researcher driven; the impetus for the creation of the story comes from the researcher and not the narrator. In recent years there has been exponential growth in illness narratives created by individuals, of their own volition, and made available for others to read in print or as Internet accounts. We sought to determine whether it was possible to identify such material for use as research data to explore the subject of living with the terminal illness amyotrophic lateral sclerosis/motor neuron disease—th...

Primary Neurons vs PC12 cells for Compound Testing

Neuromics — Sat, 07 Jan 2012 16:37:00 +0100

This publication compares PC12 Cells vs E18 Primary Cortical Neurons. The cells showed permeability to some key compounds where the Neurons did not. This demonstrates the importance of including primary neurons in compound testing assays for Neuro-disease research: Wei Zhang , Radhia Benmohamed, Anthony C. Arvanites, Richard I. Morimoto, Robert J. Ferrante, Donald R. Kirsch, Richard B. Silverman. Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells. Bioorganic & Medicinal Chemistry. Elsevier Ltd. All rights reserved.doi:10.1016/j.bmc.2011.11.039.Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA...

Stephen Hawking to give 70th birthday lecture 'A brief history of mine'

Guardian Unlimited Science — Fri, 06 Jan 2012 18:10:26 +0100

Hawking's rare public lecture on Sunday will be the star turn of a symposium in Cambridge celebrating his workThey came to honour one of their own and celebrate the life of the world's most famous living scientist, on an occasion few imagined they would see.The festivities around Professor Stephen Hawking's 70th birthday saw eminent physicists from around the globe descend on Cambridge to discuss science at the edge of understanding.The Cambridge cosmologist has worked on the inflation of the early universe and a quantum theory of gravity, and famously suggested that black holes emit radiation and so slowly disappear.But his fame has brought his field to a vast audience beyond the realms of academia. A Brief History of Time has reportedly sold more than 10m copies worldwide – more than M...

Exercise and amyotrophic lateral sclerosis

Neurological Sciences — Fri, 06 Jan 2012 16:47:40 +0100

Abstract Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease in which much burden is geared towards end-of-life care. Particularly in the earlier stages of ALS, many people have found both physiological and psychological boosts from various types of physical exercise for disused muscles. Proper exercise is important for preventing atrophy of muscles from disuse—a key for remaining mobile for as long as possible—and as long as it is possible to exercise comfortably and safely, for preserving cardiovascular fitness. However, the typical neuromuscular patient features a great physical inactivity and disuse weakness, and for that reason many controversial authors have contested exercise in these patients during years, especially in ALS ...

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Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p

Acta Neuropathologica — Fri, 06 Jan 2012 16:44:36 +0100

Abstract Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4%) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individu...

Respiratory therapies for ALS: A primer

Muscle and Nerve — Fri, 06 Jan 2012 05:00:00 +0100

AbstractRespiratory complications are a common cause of morbidity and mortality in amyotrophic lateral sclerosis (ALS). Treatment of respiratory insufficiency with noninvasive ventilation (NIV) improves ALS patients' quality of life and survival. Evidence‐based practice guidelines for the management of ALS patients recommend treatment of respiratory insufficiency with NIV as well as consideration of insufflation/exsufflation to improve clearance of airway secretions. Despite these recommendations respiratory therapies remain underutilized. In this review we provide a practical guide for the clinician to prescribe and manage respiratory therapies for the patient with ALS. © 2012 Wiley‐Liss, Inc. (Source: Muscle and Nerve)

EMGs of the flexor digitorum profundus muscle are useful for the diagnosis of inclusion body myositis

Muscle and Nerve — Fri, 06 Jan 2012 05:00:00 +0100

Conclusion:Low‐amplitude MUPs in the FDP muscle indicate the presence of an advanced myopathy in this muscle that was extremely weak for all subjects. Examining the FDP muscle would reduce the chance of misdiagnosing IBM as ALS. © 2012 Wiley‐Liss, Inc. (Source: Muscle and Nerve)

Optineurin mutations in Japanese amyotrophic lateral sclerosis

Journal of Neurology, Neurosurgery and Psychiatry — Fri, 06 Jan 2012 05:00:00 +0100

Recently, through homozygosity mapping followed by sequencing of candidate genes in the linkage region, Maruyama et al have discovered that OPTN is a causative gene for amyotrophic lateral sclerosis (ALS).1 They examined a total of 689 Japanese ALS subjects (92 with familial ALS (fALS), including 16 from consanguineous marriages, and 597 with sporadic ALS (sALS)) and identified three types of OPTN mutations.1 The first is a homozygous deletion of exon 5 in two siblings from a consanguineous family. The second is a homozygous nonsense mutation (p.Q398X) in a patient from another consanguineous family. The same homozygous mutation has been found in a sALS subject. The third is a heterozygous missense mutation (p.E478G) in two pairs of siblings from unrelated families. A functional study of p...

Birth Cohort Effects in Neurological Diseases: Amyotrophic Lateral Sclerosis, Parkinson’s Disease and Multiple Sclerosis

Neuroepidemiology — Thu, 05 Jan 2012 23:00:00 +0100

Neuroepidemiology 2012;38:56–63 (DOI:10.1159/000334632) (Source: Neuroepidemiology)

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Elevated levels of IFNγ and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis

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

Conclusion: These findings in sporadic ALS cases, which are consistent with the observation made in ALS experimental models, propose that the IFNγ‐triggered LIGHT/LT‐βR‐mediated death pathway may contribute to human ALS pathogenesis. (Source: European Journal of Neurology)

An in vitro spinal cord slice preparation for recording from lumbar motoneurons of the adult mouse

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

The development of central nervous system slice preparations for electrophysiological studies has led to an explosion of knowledge of neuronal properties in health and disease. Studies of spinal motoneurons in these preparations, however, have been largely limited to the early postnatal period, as adult motoneurons are vulnerable to the insults sustained by the preparation. We therefore sought to develop an adult spinal cord slice preparation that permits recording from lumbar motoneurons. To accomplish this, we empirically optimized the composition of solutions used during preparation in order to limit energy failure, reduce harmful ionic fluxes, mitigate oxidative stress, and prevent excitotoxic cell death. In addition to other additives, this involved the use of ethyl pyruvate, which se...

Fused in sarcoma (FUS) interacts with the cytolinker protein plectin: Implications for FUS subcellular localization and function.

Experimental Cell Research — Wed, 04 Jan 2012 05:00:00 +0100

Authors: Thomsen C, Udhane S, Runnberg R, Wiche G, Ståhlberg A, Aman P Abstract Fused in sarcoma (FUS) is a multifunctional protein involved in transcriptional control, pre-mRNA processing, RNA transport and translation. The domain structure of FUS reflects its functions in gene regulation and its ability to interact with other proteins, RNA and DNA. By use of a recombinant fragment of FUS in pull-down experiments followed by mass spectrometry analysis we have identified a novel interaction between the FUS N-terminal and the cytolinker plectin. An in situ proximity ligation assay confirmed that FUS-plectin interactions take place in the cytoplasm of cells. Furthermore, plectin deficient cells showed an altered subcellular localization of FUS and a deregulated expression of mRNAs b...

Conjugal amyotrophic lateral sclerosis.

Baylor University Medical Center Proceedings — Sun, 01 Jan 2012 05:00:00 +0100

We report a case of conjugal ALS encountered in our outpatient neurology clinic. PMID: 22275781 [PubMed - in process] (Source: Baylor University Medical Center Proceedings)

Stephen Hawking at 70: still the brightest star in the scientific universe

Guardian Unlimited Science — Sun, 01 Jan 2012 00:05:17 +0100

As the author of A Brief History of Time approaches 70, eminent former students celebrate an awe-inspiring intellect still pushing at the frontiers of physicsBERNARD CARR Professor of mathematics and astronomy, Queen Mary, University of London. Stephen Hawking's PhD student 1972-75Stephen's discovery in 1974 that black holes emit thermal radiation due to quantum effects was one of the most important results in 20th-century physics. This is because it unified three previously disparate areas of physics – quantum theory, general relativity and thermodynamics. Like all such unifying ideas, it is so beautiful that it almost has to be true, even though it has still not been experimentally confirmed. The renowned physicist John Wheeler once told me that just talking about it was like "rolling ...

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Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis

Acta Neuropathologica — Sat, 31 Dec 2011 06:37:13 +0100

Abstract While cognitive deficits are increasingly recognized as common symptoms in amyotrophic lateral sclerosis (ALS), the underlying histopathologic basis for this is not known, nor has the relevance of neuroinflammatory mechanisms and microglial activation to cognitive impairment (CI) in ALS been systematically analyzed. Staining for neurodegenerative disease pathology, TDP-43, and microglial activation markers (CD68, Iba1) was performed in 102 autopsy cases of ALS, and neuropathology data were related to clinical and neuropsychological measures. ALS with dementia (ALS-D) and ALS with impaired executive function (ALS-Ex) patients showed significant microglial activation in middle frontal and superior or middle temporal (SMT) gyrus regions, as well as significant neuron...

Cytokinetics takes a swing at Lou Gehrig's disease

bizjournals.com Health Care:Hospitals headlines — Thu, 29 Dec 2011 21:11:38 +0100

Cytokinetics Inc.’s 14-year history is marked by turns — out of cancer and into muscle programs — and a key heart failure drug partnership with biotech giant Amgen Inc. But the South San Francisco company (NASDAQ:CYTK) hasn’t yet taken a drug into the final of three phases of clinical trials, much less brought a drug to market. Whether Cytokinetics reaches that ultimate goal could rest in the outcome of a mid-stage trials in a tough disease, amyotrophic lateral sclerosis — also known as Lou Gehrig’s disease... (Source: bizjournals.com Health Care:Hospitals headlines)

Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons.

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

Authors: Hideyama T, Yamashita T, Aizawa H, Tsuji S, Kakita A, Takahashi H, Kwak S Abstract Amyotrophic lateral sclerosis (ALS) is the most common adult-onset fatal motor neuron disease. In spinal motor neurons of patients with sporadic ALS, normal RNA editing of GluA2, a subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, is inefficient. Adenosine deaminase acting on RNA 2 (ADAR2) specifically mediates RNA editing at the glutamine/arginine (Q/R) site of GluA2 and motor neurons expressing Q/R site-unedited GluA2 undergo slow death in conditional ADAR2 knockout mice. Therefore, investigation into whether inefficient ADAR2-mediated GluA2 Q/R site-editing occurs universally in motor neurons of patients with ALS would provide insight into the pathoge...

Sural nerve pathology in ALS patients: a single-centre experience

Neurological Sciences — Tue, 27 Dec 2011 17:01:51 +0100

Abstract Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of upper and lower motor neurons. Sensory involvement is thought not to be a feature of ALS. We reviewed 17 cases of sural nerve biopsies performed in a large cohort of ALS patients referred to our centre over a 23-year period. More than two-third of biopsies revealed a variable degree of axonal loss. In one case, pathological findings suggested the concomitant presence of an inherited neuropathy, subsequently confirmed by genetic evaluation. In another case, pathological and neurographic data were similar to those of an inflammatory demyelinating neuropathy, but the clinical course corroborated the diagnosis of ALS. Our data confirm that sensory nerve involvement may be found in ALS patient...

A yeast functional screen predicts new candidate ALS disease genes [Neuroscience]

Proceedings of the National Academy of Sciences — Tue, 27 Dec 2011 05:00:00 +0100

Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 ...

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Developmental Expression Pattern of Hspb8 mRNA in the Mouse Brain: Analysis Through Online Databases

Tue, 27 Dec 2011 05:00:00 +0100

In conclusion, Hspb8 mRNA is constitutively expressed in specific brain structures across ontogeny, so that eventually they could be affected by the malfunction or deregulation of this molecule. Anat Rec,, 2011. © 2011 Wiley Periodicals, Inc. (Source: The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology)

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis.

Experimental Neurology — Tue, 27 Dec 2011 05:00:00 +0100

Authors: Cosottini M, Pesaresi I, Piazza S, Diciotti S, Cecchi P, Fabbri S, Carlesi C, Mascalchi M, Siciliano G Abstract The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with def...

Homozygous SMN2 Deletion is a Major Risk Factor among Twenty-Five Korean Sporadic Amyotrophic Lateral Sclerosis Patients.

Yonsei Medical Journal — Tue, 27 Dec 2011 03:58:47 +0100

Conclusion: The homozygous SMN2 deletion (2 : 0) was statistically more frequent and associated with earlier onset age and lower MRC scale in Korean sALS patients. These suggest that SMN2 deletion may be one of the factors associated with susceptibility to and severity of sALS in a Korean population. PMID: 22187232 [PubMed - in process] (Source: Yonsei Medical Journal)

The risk to relatives of patients with sporadic amyotrophic lateral sclerosis

Brain — Mon, 26 Dec 2011 05:00:00 +0100

Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons with a median survival of 2 years. Most patients have no family history of amyotrophic lateral sclerosis, but current understanding of such diseases suggests there should be an increased risk to relatives. Furthermore, it is a common question to be asked by patients and relatives in clinic. We therefore set out to determine the risk of amyotrophic lateral sclerosis to first degree relatives of patients with sporadic amyotrophic lateral sclerosis attending a specialist clinic. Case records of patients with sporadic amyotrophic lateral sclerosis seen at a tertiary referral centre over a 16-year period were reviewed, and pedigree structures extracted. All individuals who had originally presented with sporadic amyotr...

Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis

Brain — Mon, 26 Dec 2011 05:00:00 +0100

Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and ...

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Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis

Brain — Mon, 26 Dec 2011 05:00:00 +0100

Amyotrophic lateral sclerosis as a system failure is a concept supported by the finding of consistent extramotor as well as motor cerebral pathology. The functional correlates of the structural changes detected using advanced magnetic resonance imaging techniques such as diffusion tensor imaging and voxel-based morphometry have not been extensively studied. A group of 25 patients with amyotrophic lateral sclerosis was compared to healthy control subjects using a multi-modal neuroimaging approach comprising T1-weighted, diffusion-weighted and resting-state functional magnetic resonance imaging. Using probabilistic tractography, a grey matter connection network was defined based upon the prominent corticospinal tract and corpus callosum involvement demonstrated by white matter tract-based sp...

Effect of prolonged riluzole exposure on cultured motoneurons in a mouse model of ALS

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

Riluzole is the only FDA-approved drug to treat amyotrophic lateral sclerosis, but its long-term effects on motoneurons are unknown. Therefore, we treated primary mouse spinal cord cultures with 2 μM riluzole for 4–9 days and then used whole cell patch clamp to record the passive and active properties of both wild-type and SOD1G93A motoneurons. At this concentration, riluzole blocks >50% of the sodium component of a persistent inward current that plays a major role in determining motoneuron excitability. Prolonged riluzole treatment significantly decreased the amplitude of the persistent inward current. This effect was specific for SOD1G93A motoneurons, where the amplitude decreased by 55.4%. In addition, prolonged treatment hyperpolarized the resting membrane potential as well...

Subsequent Risks of Parkinson Disease in Patients with Autoimmune and Related Disorders: A Nationwide Epidemiological Study from Sweden.

Neuro-Degenerative Diseases — Fri, 23 Dec 2011 05:00:00 +0100

Conclusions: A 33% overall excess risk of PD was noted among patients with an autoimmune disorder; the risk was increased during the first 10 years of follow-up after hospitalization of autoimmune disorders. PMID: 22205172 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)

Coping strategies in relation to quality of life in amyotrophic lateral sclerosis

Muscle and Nerve — Fri, 23 Dec 2011 03:01:08 +0100

Conclusions:The relationships between some coping strategies and certain dimensions of HRQoL are shown. We now understand the usefulness of focusing on coping strategies to improve HRQoL in ALS. Muscle Nerve 45: 131–134, 2012 (Source: Muscle and Nerve)

Validation of a new strength measurement device for amyotrophic lateral sclerosis clinical trials

Muscle and Nerve — Fri, 23 Dec 2011 03:00:58 +0100

Conclusions:ATLIS is convenient for patients and evaluators, produces precise strength measurements, and is easily moved between examining rooms. Muscle Nerve 45: 81–85, 2012 (Source: Muscle and Nerve)

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ADME-Guided Design and Synthesis of Aryloxanyl Pyrazolone Derivatives To Block Mutant Superoxide Dismutase 1 (SOD1) Cytotoxicity and Protein Aggregation: Potential Application for the Treatment of Amyotrophic Lateral Sclerosis

Journal of Medicinal Chemistry — Thu, 22 Dec 2011 11:57:55 +0100

Journal of Medicinal ChemistryDOI: 10.1021/jm2014277 (Source: Journal of Medicinal Chemistry)

Neuropathology and omics in motor neuron diseases

Neuropathology — Thu, 22 Dec 2011 05:00:00 +0100

Motor neuron diseases, including amyotrophic lateral sclerosis (ALS), are devastating disorders and effective therapies have not yet been established. One of the reasons for this lack of therapeutics, especially in sporadic ALS (SALS), is attributed to the absence of excellent disease models reflecting its pathology. For this purpose, identifying important key molecules for ALS pathomechanisms and developing disease models is crucial, and omics approaches, including genomics, transcriptomics and proteomics, have been employed. In particular, transcriptome analysis using cDNA microarray is the most popular omics approach and we have previously identified dynactin‐1 as an important molecule downregulated in the motor neurons of SALS patients from the early stage of the disease. Dynactin‐...

Grafting Of Human Spinal Stem Cells Into ALS Rats Best With Immunosuppressant Combination

Health News from Medical News Today — Wed, 21 Dec 2011 08:00:00 +0100

A team of researchers grafting human spinal stem cells into rats modeled with amyotrophic lateral sclerosis (ALS), also known as "Lou Gehrig's Disease," a degenerative, lethal, neuromuscular disease, have tested four different immunosuppressive protocols aimed at determining which regimen improved long-term therapeutic effects. Their study demonstrated that a combined, systematically delivered immunosuppression regimen of two drugs significantly improved the survival of the human spinal stem cells... (Source: Health News from Medical News Today)

Mutation analysis of VCP in familial and sporadic amyotrophic lateral sclerosis.

Neurobiology of Aging — Wed, 21 Dec 2011 05:00:00 +0100

Authors: Williams KL, Solski JA, Nicholson GA, Blair IP Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the motor cortex, brain stem and spinal cord. Mutations in the valosin-containing protein gene (VCP) were recently described in ALS families. Some of these families included diagnoses of other clinical features including frontotemporal dementia, Paget's disease, inclusion body myopathy, Parkinsonism and limb weakness. We sought to determine the prevalence of VCP mutations in Australian familial (n = 131) and sporadic (n = 48) ALS cohorts diagnosed with classic ALS. No mutations were identified indicating that VCP mutations are not a common cause of classic ALS among Australian cases with ...

Pain in Amyotrophic Lateral Sclerosis: a psychological perspective

Neurological Sciences — Mon, 19 Dec 2011 16:51:52 +0100

Abstract Pain in Amyotrophic Lateral Sclerosis is often underestimated and untreated by clinicians and few studies have investigated its specific features and impact. Pain experience was investigated with the Italian Questionnaire of Pain, together with the McGill Quality of Life Questionnaire for quality of life (QoL), at a baseline and at a 4-month follow-up. About half of ALS patients reported pain, described as nagging, sore, annoying, boring and exhausting, with periodic but enduring episodes. Pain was related with QoL and its intensity was able to predict QoL worsening. Obtained results indicate the importance of clinical investigation of pain in ALS patients and of the intervention with anti-pain treatment whenever necessary. Content Type Journal ArticleCategory...

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Grafting of human spinal stem cells into ALS rats best with immunosuppressant combination

EurekAlert! - Medicine and Health — Mon, 19 Dec 2011 05:00:00 +0100

(Cell Transplantation Center of Excellence for Aging and Brain Repair) Researchers grafting human spinal stem cells into rats modeled with amyotrophic lateral sclerosis (ALS) tested four immunosuppressive protocols to determine which regimen improved long-term therapeutic effects. Combined, systematically delivered immunosuppression regimens of tacrolimus (FK506) and mycophenolate significantly improved the survival of transplanted human spinal stem cells. While the two in combination were most effective and led to a robust graft survival three weeks after grafting, a longer half-life for mycophenolate may have been responsible. (Source: EurekAlert! - Medicine and Health)

An MND/ALS phenotype associated with C9orf72 repeat expansion: Abundant p62‐positive, TDP‐43‐negative inclusions in cerebral cortex, hippocampus and cerebellum but without associated cognitive decline

Neuropathology — Mon, 19 Dec 2011 05:00:00 +0100

The transactive response DNA binding protein (TDP‐43) proteinopathies describe a clinico‐pathological spectrum of multi‐system neurodegeneration that spans motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and frontotemporal lobar degeneration (FTLD). We have identified four male patients who presented with the clinical features of a pure MND/ALS phenotype (without dementia) but who had distinctive cortical and cerebellar pathology that was different from other TDP‐43 proteinopathies. All patients initially presented with weakness of limbs and respiratory muscles and had a family history of MND/ALS. None had clinically identified cognitive decline or dementia during life and they died between 11 and 32 months after symptom onset. Neuropathological investigation revealed ...

CuII(atsm) Prolongs Survival of ALS Mice [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 16 Dec 2011 05:00:00 +0100

This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had ...

Neurodegenerative disease: Novel ALS therapy shows promise in Phase II

Nature Reviews Drug Discovery — Fri, 16 Dec 2011 05:00:00 +0100

Nature Reviews Drug Discovery 11, 22 (2012). doi:10.1038/nrd3634 Author: Sarah Crunkhorn Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by degeneration of the upper and lower motor neurons, causing muscle weakness and atrophy throughout the body. The only approved disease-modifying treatment for ALS is riluzole (which has effects on both the excitatory amino (Source: Nature Reviews Drug Discovery)

Erratum to: Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset

European Journal of Nuclear Medicine and Molecular Imaging — Thu, 15 Dec 2011 16:49:07 +0100

Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s00259-011-2029-0Authors Angelina Cistaro, Positron Emission Tomography Center IRMET S.p.A, Turin, ItalyMaria Consuelo Valentini, Department of Neuroradiology, CTO Hospital, Turin, ItalyAdriano Chiò, Department of Neuroscience, ALS Center, University of Turin, Turin, ItalyFlavio Nobili, Department of Neurosciences, Clinical Neurophysiology Unit, Ophthalmology and Genetics, University of Genoa, Genoa, ItalyAndrea Calvo, Department of Neuroscience, ALS Center, University of Turin, Turin, ItalyCristina Moglia, Department of Neuroscience, ALS Center, University of Turin, Turin, ItalyAnna Montuschi, Department of Neuroscience, ALS Center, University of Turin, Turin, ItalySilvia Morbelli, Department of Internal Medicine, Nucle...

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Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats

Journal of Clinical Investigation — Wed, 14 Dec 2011 08:26:02 +0100

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. All of these rats developed progressive paralysis reminiscent of ALS when the transgene was switched on. Rats expressing mutant TDP-43 in motor neurons alone lost...

Modeling human neurodegenerative diseases in transgenic systems

Human Genetics — Tue, 13 Dec 2011 17:05:00 +0100

Abstract Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies ...

[Comment] What is repeated in ALS and FTLD

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

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are part of a disease spectrum that is clinically, pathologically, and genetically heterogeneous. Since 2006, there have been several reports of linkage of autosomal-dominant adult-onset FTLD-ALS to a locus at 9p13.2–21.3. and sporadic ALS in some but not all populations. This finding underlies the diversity in the causes of ALS. A non-coding defect was expected because all known and predicted genes in the 9p candidate region had been sequenced by several groups (with strategies including next-generation sequencing) without the identification of mutations in coding regions. (Source: Lancet Neurology)

[Articles] A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study

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

SummaryBackgroundAmyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are extremes of a clinically, pathologically, and genetically overlapping disease spectrum. A locus on chromosome 9p21 has been associated with both disorders, and we aimed to identify the causal gene within this region.MethodsWe studied 305 patients with FTLD, 137 with ALS, and 23 with concomitant FTLD and ALS (FTLD-ALS) and 856 controls from Flanders (Belgium); patients were identified from a hospital-based cohort and were negative for mutations in known FTLD and ALS genes. (Source: Lancet Neurology)

In Rat Model Of Lou Gehrig's, Disease Progression Halted

Health News from Medical News Today — Tue, 13 Dec 2011 09:00:00 +0100

Amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease) is an incurable adult neurodegenerative disorder that progresses to paralysis and death. Genetic mutations are the cause of disease in 5% of patients with ALS. Of immense interest, Hongxia Zhou, Xu-Gang Xia, and colleagues, at Thomas Jefferson University, Philadelphia, now show that progressive neuron degeneration can be halted in a rat model of familial ALS linked to mutations in the gene that carries the instructions for making the protein TDP-43... (Source: Health News from Medical News Today)

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Physiological characterization of human muscle acetylcholine receptors from ALS patients [Neuroscience]

Proceedings of the National Academy of Sciences — Tue, 13 Dec 2011 05:00:00 +0100

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or from control denervated muscle, obtained by needle biopsy, are amenable to functional characterization by two different technical approaches: “microtransplantation” of muscle membranes into Xenopus oocytes and culture of myogenic satellite cells. Acetylcholine (ACh)-evoked currents and unitary events were characterized in oocytes and multinucleated myotubes. We found that ALS acetylcholine receptors...

The distal hereditary motor neuropathies

Journal of Neurology, Neurosurgery and Psychiatry — Tue, 13 Dec 2011 05:00:00 +0100

(dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot–Marie–Tooth disease (CMT2) and with juvenile forms of amyotrophic lateral sclerosis and hereditary spastic paraplegia. Eleven causative genes and four loci have been identified with autosomal dominant, recessive and X-linked patterns of inheritance. Despite advances in the identification of novel gene mutations, 80% of patients with dHMN have a mutation in an as-yet undiscovered gene. The causative genes have implicated proteins with diverse functions such as protein misfolding (HSPB...

The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study

Journal of Neurology, Neurosurgery and Psychiatry — Tue, 13 Dec 2011 05:00:00 +0100

Conclusion Co-morbid dementia occurs in approximately 14% of patients with a new diagnosis of ALS. Cognitive impairment, predominantly but not exclusively in the form executive dysfunction, is present in more than 40% of ALS patients who have no evidence of dementia. Cognitive impairment in ALS is not a universal feature, and its manifestations may be more heterogeneous than previously recognised. (Source: Journal of Neurology, Neurosurgery and Psychiatry)

Ultrastructural Mitochondrial Abnormalities in Patients With Sporadic Amyotrophic Lateral Sclerosis [Research Letters]

Archives of Neurology — Mon, 12 Dec 2011 05:00:00 +0100

(Source: Archives of Neurology)

Familial versus sporadic amyotrophic lateral sclerosis--a false dichotomy?

Brain — Sun, 11 Dec 2011 05:00:00 +0100

(Source: Brain)

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The risk to relatives of patients with sporadic amyotrophic lateral sclerosis

Brain — Sun, 11 Dec 2011 05:00:00 +0100

Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis

Brain — Sun, 11 Dec 2011 05:00:00 +0100

Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis

Brain — Sun, 11 Dec 2011 05:00:00 +0100

Autophagy Dysregulation in Amyotrophic Lateral Sclerosis

Brain Pathology — Sat, 10 Dec 2011 14:02:06 +0100

AbstractAutophagy is an intracellular lysosomal degradation process, which plays an important role in cell growth and development, and keeping cellular homeostasis in all eukaryotes. Autophagy has multiple physiological functions, including protein degradation, organelle turnover and response to stress. Emerging evidences support the notion that dysregulation of autophagy might be critical for pathogenesis of amyotrophic lateral sclerosis (ALS). The autophagy dysregulation in motor neurons of ALS may occur in different steps of the autophagic process. Recent studies have shown that two ALS associated proteins, TDP‐43 and superoxide dismutase 1 (SOD1), are involved in the abnormal autophagy regulation. Furthermore, it is reported that several genetic mutations in ALS disturb the autophagi...

Novel Therapeutic Approach for Neurodegenerative Pathologies: Multitarget Iron-Chelating Drugs Regulating Hypoxia-Inducible Factor 1 Signal Transduction Pathway.

Neuro-Degenerative Diseases — Fri, 09 Dec 2011 05:00:00 +0100

Authors: Weinreb O, Amit T, Mandel S, Youdim MB Abstract Our novel multimodal brain-permeable iron-chelating compounds M30 and HLA20 were demonstrated to possess neuroprotective/neurorescue activities in vitro and in vivo against several insults applicable to various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Neuroprotection by iron chelators has been widely recognized with respect to their ability to prevent reactive oxygen species generation in the Fenton reaction by sequestering redox-active iron. An additional neuroprotective mechanism of iron-chelating compounds is associated with their ability to regulate the transcriptional activator hypoxia-inducible factor 1 (HIF-1). HIF-1 is a 'master switch' being an im...

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Exome sequencing reveals SPG11 mutations causing juvenile ALS.

Neurobiology of Aging — Fri, 09 Dec 2011 05:00:00 +0100

We report here the description of a nonconsanguineous family with 2 affected individuals with a recessively inherited juvenile motor neuron disease. Exome sequencing of these 2 affected individuals led us to identify 2 compound heterozygous deletions leading to a frameshift and a premature stop codon in the SPG11 gene. One of these deletions, c.5199delA in exon 30, has not been previously reported. Interestingly, these deletions are associated with an intrafamilial phenotypic heterogeneity as one affected has atypical juvenile amyotrophic lateral sclerosis (ALS) and the other has classical hereditary spastic paraplegia with thin corpus callosum. Our findings confirm SPG11 as a genetic cause of juvenile amyotrophic lateral sclerosis and indicate that SPG11 mutations could be associated with...

The cortisol awakening response in amyotrophic lateral sclerosis is blunted and correlates with clinical status and depressive mood

Psychoneuroendocrinology — Fri, 09 Dec 2011 03:39:07 +0100

In conclusion, our findings indicate that ALS patients show a blunted CAR, correlated with disease and depression severity. (Source: Psychoneuroendocrinology)

ELISA Methodology to Quantify Astrocyte Production of Cytokines/Chemokines In Vitro

Springer protocols feed by Neuroscience — Fri, 09 Dec 2011 01:09:10 +0100

Astrocytes are intimately involved in immunological and inflammatory events occurring in the central nervous system (CNS), due to their ability to secrete and respond to a large number of immunoregulatory cytokines/chemokines such as IL-1ß, IL-6, IL-8, IL-10, IL-17, IL-27, TNF-a, TGF-ß, IFN-?, IFN-ß, CCL2, CCL3, CCL5, CXCL10, and CXCL12. Although expression of cytokines and chemokines is limited in the normal CNS, elevated expression of these proteins, as seen in disease entities such as multiple sclerosis (MS), HIV-1 associated neurocognitive disorders (HAND), Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), contributes to the development of inflammation and neuronal demise in these diseases. As a potent source of cy...

Genetically Engineered Mesenchymal Stem Cells as a Proposed Therapeutic for Huntington’s Disease

Molecular Neurobiology — Thu, 08 Dec 2011 18:25:05 +0100

Abstract There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that are fatal and difficult to treat, such as Huntington’s disease. MSC present a promising tool for cell therapy and are currently being tested in FDA-approved phase I–III clinical trials for many disorders. In preclinical studies of neurodegenerative disorders, MSC have demonstrated efficacy, when used as delivery vehicles for neural growth factors. A number of investigators have examined the potential benefits of innate MSC-secreted trophic support and augmented growth factors to support injured neurons. These include overexpression of brain-derived neurotrophic factor and glial-derived neurotrophic factor, using ...

Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis.

Neurobiology of Aging — Thu, 08 Dec 2011 05:00:00 +0100

Authors: Millecamps S, Corcia P, Cazeneuve C, Boillée S, Seilhean D, Danel-Brunaud V, Vandenberghe N, Pradat PF, Le Forestier N, Lacomblez L, Bruneteau G, Camu W, Brice A, Meininger V, Leguern E, Salachas F Abstract Mutations in UBQLN2 encoding ubiquilin-2 have recently been identified in families with dominant X-linked juvenile and adult-onset amyotrophic lateral sclerosis (ALS) and ALS/dementia. Ubiquilin-2 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients. All the previously reported UBQLN2 mutations were localized in 1 of the 12 PXX domains of ubiquilin-2 protein. We sequenced UBQLN2 in 130 French patients with familial ALS (FALS) and absence of male-to-male transmission and the PXX domain in 240 more patients with sporadic ALS (SALS)....

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Organ Donation after Cardiac Death from Withdrawal of Life Support in Patients with Amyotrophic Lateral Sclerosis

Journal of Palliative Medicine — Thu, 08 Dec 2011 04:11:34 +0100

Journal of Palliative Medicine , Vol. 0, No. 0. (Source: Journal of Palliative Medicine)

Curcumins Promote Monocytic Gene Expression Related to β-Amyloid and Superoxide Dismutase Clearance.

Neuro-Degenerative Diseases — Wed, 07 Dec 2011 05:00:00 +0100

Authors: Cashman JR, Gagliardi S, Lanier M, Ghirmai S, Abel KJ, Fiala M Abstract Neurodegenerative diseases are associated with accumulation of modified proteins or peptides including amyloid-β (Aβ) in Alzheimer's disease (AD), and misfolded superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS). Clearance of Aβ or SOD-1 by the innate immune system may be important for controlling or preventing disease onset. Curcumins restore Aβ phagocytosis by peripheral blood mononuclear cells (PBMCs) from AD patients and Aβ clearance with upregulation of key genes including MGAT3, vitamin D receptor (VDR) and Toll-like receptors (TLRs). Certain curcumins inhibit inflammatory processes of PBMCs from ALS patients. We developed an in vitro system using human monocytes from pati...

Cobalt(II) β-ketoaminato complexes as novel inhibitors of neuroinflammation.

European Journal of Pharmacology — Wed, 07 Dec 2011 05:00:00 +0100

Authors: Madeira JM, Beloukhina N, Boudreau K, Boettcher TA, Gurley L, Walker DG, McNeil WS, Klegeris A Abstract Neuroinflammation contributes to the pathogenesis of neurological disorders including stroke, head trauma, multiple sclerosis, amyotrophic lateral sclerosis as well as age-associated neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Therefore, anti-inflammatory drugs could be used to slow the progression of these diseases. We studied the anti-neuroinflammatory activity of four novel square planar cobalt(II) compounds bearing tetradentate β-ketoaminato ligands with variation in the number of CF(3) ligand substituents, as well as their corresponding unmetallated organic ligands. Cobalt (Co) complexes were consistently more active than their corre...

Neurodegeneration as a consequence of failed mitochondrial maintenance

Acta Neuropathologica — Tue, 06 Dec 2011 07:01:37 +0100

Abstract Maintaining the functional integrity of mitochondria is pivotal for cellular survival. It appears that neuronal homeostasis depends on high-fidelity mitochondria, in particular. Consequently, mitochondrial dysfunction is a fundamental problem associated with a significant number of neurological diseases, including Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and various peripheral neuropathies, as well as the normal aging process. To ensure optimal mitochondrial function, diverse, evolutionarily conserved mitochondrial quality control mechanisms are in place, including the scavenging of toxic reactive oxygen species (ROS) and degradation of damaged mitochondrial proteins, but also turnover...

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Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis

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

Abstract: Mutations in valosin-containing protein (VCP) gene, already known to be associated with the multisystemic disorder, inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD), have been recently found also in familial cases of amyotrophic lateral sclerosis (ALS). To further define the frequency of VCP mutations in ALS Italian population, we screened a cohort of 166 familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified a previously reported synonymous mutation (c.2093A>C; p.Q568Q), 2 intronic variants (c.1749-14C>T; c.2085-3C>T), and 1 nucleotide change (c.2814G>T) in the 3′ untranslated region (UTR). Bioinformatical analyses predicted no changes in splicing process or microRNA binding sites. Our results do not confirm a main co...

An Autopsy Case of Amyotrophic Lateral Sclerosis with Waldenström Macroglobulinemia and Anti-MAG Gammopathy

Karger Publishers — Sun, 04 Dec 2011 01:25:31 +0100

Case Rep Neurol 2011;3:294–300 (DOI:10.1159/000335004) (Source: Karger Publishers)

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)

The UBQLN2/p62 cellular recycling pathways in ALS and ALS‐FTD

Muscle and Nerve — Thu, 01 Dec 2011 05:00:00 +0100

AbstractRecent findings highlight a pathological and functional convergence in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS‐FTD) at the level of protein recycling and disposal. Genes linked to rare cases of familial ALS and ALS‐FTD, like UBQLN2, OPTN, SQSTM1/p62 and VCP may converge onto a unifying pathogenic pathway and thereby provide novel therapeutic targets common to a spectrum of etiologically diverse forms of ALS and ALS‐FTD. Interactions between these genes need to be further explored to understand their common molecular pathways. Future efforts should be directed towards generation and characterization of in vivo models to dissect the pathogenic mechanisms of ALS and ALS‐FTD and the role of protein degradation path...

Amyotrophic lateral sclerosis: from research to therapeutic attempts and therapeutic perspectives.

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

Authors: Contestabile A Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons which brings to muscular atrophy, paralysis and death in 3-5 years from starting symptoms. In about 10% of cases ALS is familiar and in a relevant percent of these cases, mutations of the enzyme copper-zinc superoxide dismutase 1 (SOD1) are found. Transgenic mice expressing mutated forms of SOD1 replicate with fidelity the onset and progression of the disease and have been largely used to test therapies to be translated to patients in clinical trials. Over years, many therapeutic approaches have been attempted in mice model often with significant, albeit limited, benefits on disease onset, progression and lifespan. Unfo...

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Mutational analysis of VCP gene in familial amyotrophic lateral sclerosis.

Neurobiology of Aging — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Tiloca C, Ratti A, Pensato V, Castucci A, Sorarù G, Del Bo R, Corrado L, Cereda C, D'Ascenzo C, Comi GP, Mazzini L, Castellotti B, Ticozzi N, Gellera C, Silani V, Abstract Mutations in valosin-containing protein (VCP) gene, already known to be associated with the multisystemic disorder, inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD), have been recently found also in familial cases of amyotrophic lateral sclerosis (ALS). To further define the frequency of VCP mutations in ALS Italian population, we screened a cohort of 166 familial ALS and 14 ALS-frontotemporal dementia (FTD) individuals. We identified a previously reported synonymous mutation (c.2093A>C; p.Q568Q), 2 intronic variants (c.1749-14C>T; c.2085-3C>T), and 1 nucleotid...

SIGMAR1 mutations, genetic heterogeneity at the chromosome 9p locus, and the expanding etiological diversity of amyotrophic lateral sclerosis

Annals of Neurology — Thu, 01 Dec 2011 05:00:00 +0100

(Source: Annals of Neurology)

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Annals of Neurology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractObjective:Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.Methods:We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We seque...

Cytokinetics reports positive study results of CK-2017357

Drug Development Technology — Thu, 01 Dec 2011 00:00:00 +0100

Cytokinetics' CK-2017357 drug has met all primary endpoints in the first cohort of an ongoing Phase II clinical trial in patients with amyotrophic lateral sclerosis. (Source: Drug Development Technology)

[Nutritional management in amyotrophic lateral sclerosis: A medical and ethical stake.]

Presse Medicale — Wed, 30 Nov 2011 05:00:00 +0100

Authors: Lehéricey G, Le Forestier N, Dupuis L, Gonzalez-Bermejo J, Meininger V, Pradat PF Abstract Malnutrition and dehydration are common and result from swallowing disorders secondary to degeneration of brainstem motor neurons. Recent knowledge argues in favor of the associated primary metabolism abnormalities. Though muscle atrophy, a paradoxical hypermetabolism at rest has often been observed. Hyperlipidemia and glucose intolerance are more frequent than in general population. The heterogeneity of the nutritional assessment of patients in published series is due, partially at least, to the use of disparate criteria and evaluating procedures. Weight lost is an independent negative survival prognostic factor. Overweight may be beneficial for the survival of ALS patients. A spec...

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Pathobiochemical Effect of Acylated Steryl-β-Glucoside on Aggregation and Cytotoxicity of α-Synuclein.

Neurochemical Research — Tue, 29 Nov 2011 05:00:00 +0100

This study demonstrated that ASG directly enhances aggregation and cytotoxicity of α-synuclein, which are often observed in patients with ALS/PDC. These results, using assays that replicate cytoplasmic conditions, are consistent with the molecular mechanism that cytotoxicity is caused by intracellular α-synuclein fibril formation in neuronal cells. PMID: 22124781 [PubMed - as supplied by publisher] (Source: Neurochemical Research)

Sclerosis drug could slow eye cancer growth

Pharmaceutical Technology — Tue, 29 Nov 2011 00:00:00 +0100

A drug used to treat amyotrophic lateral sclerosis, a form of motor neurone disease, has been shown to make eye tumours less likely to grow if they spread to other parts of the body, a study conducted at the Washington University School of Medicine i… (Source: Pharmaceutical Technology)

An autopsy case of SOD1-related ALS with TDP-43 positive inclusions

Neurology — Mon, 28 Nov 2011 05:00:00 +0100

(Source: Neurology)

UNC13A is a modifier of survival in amyotrophic lateral sclerosis

Neurobiology of Aging — Mon, 28 Nov 2011 05:00:00 +0100

We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. (Source: Neurobiology of Aging)

Eminent scientists and their tattoos | Feature

Guardian Unlimited Science — Sun, 27 Nov 2011 00:05:07 +0100

From DNA to dinosaurs, scientists have a surprising and secret penchant for tattoos – of a particularly cerebral natureI happen to be friends with Professor Sandeep Robert Datta, a neurobiologist at Harvard Medical School. I call him Bob. In the summer of 2007, Bob and his wife Eliza and their two boys, Jasper and Theo, came to a pool party for the birthday of my nephew Blake, and the esteemed neurobiologist splashed around in the water for hours. It was then that I noticed something on Bob's arm. He had a tattoo.The tattoo, I could see, was that most famous molecule, the twisting ladder of DNA. There was a logic to the choice, since Bob studies the DNA of fruit flies, observing how mutations to certain genes alter how their nerves develop and how they behave.When I complimented Bob on h...

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Intraspinal Injection of Human Umbilical Cord Blood-Derived Cells Is Neuroprotective in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.

Neuro-Degenerative Diseases — Sat, 26 Nov 2011 05:00:00 +0100

Conclusion: This study confirms the neuroprotective potential of human umbilical cord blood cells and encourages further investigations. PMID: 22122965 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)

Intraspinal Injection of Human Umbilical Cord Blood-Derived Cells Is Neuroprotective in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Neurodegenerative Diseases — Fri, 25 Nov 2011 13:28:58 +0100

Neurodegenerative Dis (DOI:10.1159/000331327) (Source: Neurodegenerative Diseases)

Paradoxical roles of serine racemase and D‐serine in the G93A mSOD1 mouse model of ALS

Journal of Neurochemistry — Fri, 25 Nov 2011 13:22:49 +0100

AbstractD‐serine is an endogenous neurotransmitter that binds to the NMDA receptor, thereby increasing the affinity for glutamate, and the potential for excitotoxicity. The primary source of D‐serine in vivo is enzymatic racemization by serine racemase (SR). Regulation of D‐serine in vivo is poorly understood, but is thought to involve a combination of controlled production, synaptic reuptake by transporters, and intracellular degradation by D‐amino acid oxidase (DAO). However, SR itself possesses a well‐characterized eliminase activity which effectively degrades D‐serine as well. D‐serine is increased two‐fold in spinal cords of G93A SOD1 mice – the standard model of amyotrophic lateral sclerosis (ALS). ALS mice with SR disruption show earlier symptom onset, but survive ...

Paradoxical roles of serine racemase and d‐serine in the G93A mSOD1 mouse model of amyotrophic lateral sclerosis

Journal of Neurochemistry — Fri, 25 Nov 2011 05:00:00 +0100

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07601.xAbstractd‐Serine is an endogenous neurotransmitter that binds to the NMDA receptor, thereby increasing the affinity for glutamate, and the potential for excitotoxicity. The primary source of d‐serine in vivo is enzymatic racemization by serine racemase (SR). Regulation of d‐serine in vivo is poorly understood, but is thought to involve a combination of controlled production, synaptic reuptake by transporters, and intracellular degradation by d‐amino acid oxidase (DAO). However, SR itself possesses a well‐characterized eliminase activity, which effectively degrades d‐serine as well. d‐Serine is increased two‐fold in spinal cords of G93A Cu,Zn‐superoxide dismutase (SOD1) mice – the standard model of amyotrophic latera...

Consumer Information on: NeuRx DPS?, Diaphragm Pacing System - H100006

Food and Drug Adminstration (FDA): CDRHNew — Wed, 23 Nov 2011 05:00:00 +0100

The NeuRx Diaphragm Pacing System (DPS)? is a percutaneous, intramuscular, diaphragm motor point stimulating device intended for use in amyotrophic lateral sclerosis (ALS) patients with a stimulatable diaphragm (both right and left portions) as... (Source: Food and Drug Adminstration (FDA): CDRHNew)

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NeuRx DPS™, Diaphragm Pacing System

Medical Device Approvals — Wed, 23 Nov 2011 05:00:00 +0100

The NeuRx Diaphragm Pacing System (DPS)™ is a percutaneous, intramuscular, diaphragm motor point stimulating device intended for use in amyotrophic lateral sclerosis (ALS) patients with a stimulatable diaphragm (both right and left portions) as... (Approved: 9/28/2011) (Source: Medical Device Approvals)

UNC13A is a modifier of survival in amyotrophic lateral sclerosis.

Neurobiology of Aging — Wed, 23 Nov 2011 05:00:00 +0100

Accumulation of insoluble forms of FUS protein correlates with toxicity in Drosophila.

Neurobiology of Aging — Wed, 23 Nov 2011 05:00:00 +0100

Authors: Miguel L, Avequin T, Delarue M, Feuillette S, Frébourg T, Campion D, Lecourtois M Abstract Recently, the fused in sarcoma/translated in liposarcoma (FUS) protein has been identified as a major constituent of nuclear and/or cytoplasmic ubiquitin-positive inclusions in patients with frontotemporal lobar degeneration or amyotrophic lateral sclerosis. The molecular mechanisms underlying FUS toxicity are currently not understood. To address aspects of FUS pathogenesis in vivo, we have generated new Drosophila transgenic models expressing a full-length wild-type isoform of human FUS protein. We found that when expressed in retinal cells, FUS proteins are mainly recovered as soluble forms, and their overexpression results in a mild eye phenotype, with malformed interommatidial b...

Primary lateral sclerosis: Upper‐motor‐predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration – immunohistochemical and biochemical analyses of TDP‐43

Neuropathology — Tue, 22 Nov 2011 12:58:55 +0100

In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper‐motor‐predominant amyotrophic lateral sclerosis with FTLD‐TDP. (Source: Neuropathology)

Novel ALS Drug Slows Symptom Progression, Reduces Mortality In Phase 2 Trial

Health News from Medical News Today — Tue, 22 Nov 2011 08:00:00 +0100

Treatment with dexpramipexole - a novel drug believed to prevent dysfunction of mitochondria, the subcellular structures that provide most of a cell's energy - appears to slow symptom progression in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Promising results of a phase 2 trial of dexpramipexole are receiving advance online publication in Nature Medicine. Some preliminary results of the study were presented at the 2009 International Symposium on ALS/MND and the 2010 American Academy of Neurology annual meeting... (Source: Health News from Medical News Today)

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Epitope mapping of antibodies against TDP-43 and detection of protease-resistant fragments of pathological TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

Biochemical and Biophysical Research communications — Tue, 22 Nov 2011 05:00:00 +0100

Authors: Tsuji H, Nonaka T, Yamashita M, Suzukake M, Kametani F, Akiyama H, Mann DM, Tamaoka A, Hasegawa M Abstract TAR DNA-binding protein of 43kDa (TDP-43) is the major component of the intracellular inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we show that both monoclonal (60019-2-Ig) and polyclonal (10782-2-AP) anti-TDP-43 antibodies recognize amino acids 203-209 of human TDP-43. The monoclonal antibody labeled human TDP-43 by recognizing Glu204, Asp205 and Arg208, but failed to react with mouse TDP-43. The antibodies stained the abnormally phosphorylated C-terminal fragments of 23-24kDa in addition to normal TDP-43 in ALS and FTLD brains. Immunoblot analysis after protease treatment demonstrated that the epitope of the a...

Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathology

Acta Neuropathologica — Mon, 21 Nov 2011 18:09:06 +0100

Abstract Research into amyotrophic lateral sclerosis (ALS) has been stimulated by a series of genetic and molecular pathology discoveries. The hallmark neuronal cytoplasmic inclusions of sporadic ALS (sALS) predominantly comprise a nuclear RNA processing protein, TDP-43 encoded by the gene TARDBP, a discovery that emerged from high throughput analysis of human brain tissue from patients with frontotemporal dementia (FTD) who share a common molecular pathology with ALS. The link between RNA processing and ALS was further strengthened by the discovery that another genetic locus linking familial ALS (fALS) and FTD was due to mutation of the fused in sarcoma (FUS) gene. Of potentially even greater importance it emerges that TDP-43 accumulation and inclusion formation characteris...

Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor {kappa}B-mediated pathogenic pathways

The Journal of Experimental Medicine — Mon, 21 Nov 2011 05:00:00 +0100

In this study, we report that TDP-43 and nuclear factor B (NF-B) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-B activity, reduced denervation ...

ALS Responds to Modified Parkinson Drug (CME/CE)

MedPage Today Geriatrics — Sun, 20 Nov 2011 22:39:54 +0100

(MedPage Today) -- Patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, showed signs in a small dose-ranging study that an investigational agent derived from the Parkinson's disease drug pramipexole might slow the loss of muscle strength and function, researchers said. (Source: MedPage Today Geriatrics)

Novel ALS drug slows symptom progression, reduces mortality in phase 2 trial

EurekAlert! - Medicine and Health — Sun, 20 Nov 2011 05:00:00 +0100

(Massachusetts General Hospital) Results of a phase 2 clinical trial indicate that treatment with dexpramipexole -- a novel drug believed to prevent dysfunction of mitochondria, the subcellular structures that provide most of a cell's energy -- appears to slow symptom progression in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). (Source: EurekAlert! - Medicine and Health)

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The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis

Nature Medicine — Sun, 20 Nov 2011 05:00:00 +0100

Authors: Merit Cudkowicz, Michael E Bozik, Evan W Ingersoll, Robert Miller, Hiroshi Mitsumoto, Jeremy Shefner, Dan H Moore, David Schoenfeld, James L Mather, Donald Archibald, Mary Sullivan, Craig Amburgey, Juliet Moritz & Valentin K Gribkoff Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron dysfunction and loss, rapidly progressive muscle weakness, wasting and death. Many factors, including mitochondrial dysfunction, may contribute to ALS pathogenesis. Riluzole, which has shown only modest benefits in a measure of survival time without demonstrated effects on muscle strength or function, is the only approved treatment for ALS. We tested the putative mitochondrial modulator dexpramipexole (KNS-760704; (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazol...

PGC‐1α protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model

Muscle and Nerve — Sun, 20 Nov 2011 02:23:58 +0100

Conclusion: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC‐1α/G93A DL mice may contribute to neuronal protection. Muscle Nerve 2011 (Source: Muscle and Nerve)

The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate.

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

Authors: Koh SH, Baik W, Noh MY, Cho GW, Kim HY, Kim KS, Kim SH Abstract Amyotrophic lateral sclerosis (ALS) is caused by motor neuron death. The relationship between the prognosis of ALS patients and the function of their bone marrow mesenchymal stromal cells (BM-MSCs) is unclear. We designed this study to assess the correlation between the progression rate of the ALS Functional Rating Scale-revised version (ΔFS), which is reported to predict prognosis, and the pluripotency and trophic factor secreting capacity of ALS patients' BM-MSCs. We evaluated ΔFS in 23 ALS patients and isolated BM-MSCs from those patients and five healthy people. Levels of Nanog, Oct-4, and Nestin mRNA were examined to evaluate pluripotency, and levels of BDNF, ECGF1, bFGF-2, HGF, IGF-1, PGF, TGF-1β, SDF...

Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans

Acta Neuropathologica — Fri, 18 Nov 2011 17:28:28 +0100

Abstract The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer’s disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43...

p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS

Acta Neuropathologica — Fri, 18 Nov 2011 17:28:27 +0100

Abstract Neuronal cytoplasmic inclusions (NCIs) containing phosphorylated TDP-43 (p-TDP-43) are the pathological hallmarks of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and FTLD-TDP. The vast majority of NCIs in the brain and spinal cord also label for ubiquitin and p62, however, we have previously reported a subset of TDP-43 proteinopathy patients who have unusual and abundant p62 positive, TDP-43 negative inclusions in the cerebellum and hippocampus. Here we sought to determine whether these cases carry the hexanucleotide repeat expansion in C9orf72. Repeat primer PCR was performed in 36 MND/ALS, FTLD-MND/ALS and FTLD-TDP cases and four controls. Fourteen individuals with the repeat expansion were detected. In all the 14 expansion mutation cases there we...

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Quality of life and measures of quality of life in patients with neuromuscular disorders

Muscle and Nerve — Fri, 18 Nov 2011 05:00:00 +0100

AbstractThis review provides the reader with an overview of quality of life (QOL) and QOL measures in neuromuscular disorders. We discuss the characteristics of QOL measures used in neuromuscular research, highlighting differences between generic versus disease‐specific and global versus health‐related QOL instruments. The phenomenon of response shift is reviewed. Commonly used QOL instruments are reviewed for amyotrophic lateral sclerosis, muscle diseases, myasthenia gravis and polyneuropathy. We also review some of what is known about QOL for patients with these neuromuscular disorders. © 2011 Wiley‐Liss, Inc. (Source: Muscle and Nerve)

Research advances in gene therapy approaches for the treatment of amyotrophic lateral sclerosis.

Cellular and Molecular Life Sciences : CMLS — Fri, 18 Nov 2011 05:00:00 +0100

Authors: Nizzardo M, Simone C, Falcone M, Riboldi G, Rizzo F, Magri F, Bresolin N, Comi GP, Corti S Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons that causes progressive muscle weakness, paralysis, and premature death. No effective therapy is available. Research in the motor neuron field continues to grow, and recent breakthroughs have demonstrated the possibility of completely achieving rescue in animal models of spinal muscular atrophy, a genetic motor neuron disease. With adeno-associated virus (AAV) vectors, gene transfer can be achieved with systemic non-invasive injection and minimal toxicity. In the context of this success, we review gene therapy approaches for ALS, considering what has been done and the possible fut...

New Candidate Gene For Lou Gehrig's Disease Revealed By Genetic Screening In Yeast

Health News from Medical News Today — Thu, 17 Nov 2011 09:00:00 +0100

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a universally fatal neurodegenerative disease. Mutations in two related proteins, TDP-43 and FUS, cause some forms of ALS. Specifically, these two proteins are RNA-binding proteins that connect to RNA to regulate the translation of proteins and other cellular functions such as RNA splicing and editing. In a new study, researchers at the Perelman School of Medicine at the University of Pennsylvania discovered additional human genes with properties similar to TDP-43 and FUS that might also contribute to ALS... (Source: Health News from Medical News Today)

Superoxide dismutase 1 encoding mutations linked to ALS adopts a spectrum of misfolded states

Molecular Neurodegeneration — Thu, 17 Nov 2011 05:00:00 +0100

Conclusions: Our studies demonstrate how different methods of detecting misfolding and aggregation of mutant SOD1 reveal different forms of aberrantly folded protein. Immunological and biochemical methods can be used in combination to detect soluble and insoluble misfolded forms of mutant SOD1. Our findings support the view that mutant SOD1 can adopt multiple misfolded conformations with the potential that different structural variants mediate different aspects of fALS. (Source: Molecular Neurodegeneration)