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Dimerization in GPCR mobility and signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Many types of cell surface as well as intracellular DNA-binding receptors exist and function as dimers; formation of homodimers or heterodimers appears to not only provide molecular mechanisms for agonist-induced activation but also increase specificity of ligand recognition and versatility of downstream signaling. G-protein-coupled receptors (GPCRs) were long thought to be an exception, but in recent years a lot of evidence has accumulated that GPCRs also can form dimers, even though it is far from certain when and where they actually do so under physiological conditions. Dimerization of GPCRs does not generally seem ...
Source: Current Opinion in Pharmacology - November 10, 2009 Category: Drugs & Pharmacology Authors: Lohse MJ Tags: Curr Opin Pharmacol Source Type: journals

Recent advances in bioluminescence resonance energy transfer technologies to study GPCR heteromerization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The field of G protein-coupled receptor (GPCR) research has undergone a transformation in recent years due to the notion of heteromerization. In order to progress our understanding of the functional implications of this phenomenon, as well as its applicability across the diversity of GPCR subtypes, we need to continually look to improve the technologies we use to evaluate protein-protein interactions in as near a physiological setting as possible. The bioluminescence resonance energy transfer (BRET) technology has been intimately associated with the study of GPCR-GPCR interactions for the past ten years, and over this ...
Source: Current Opinion in Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Ayoub MA, Pfleger KD Tags: Curr Opin Pharmacol Source Type: journals

Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The repertoire of signal transduction pathways activated by dopamine in brain includes the increase of intracellular calcium. However the mechanism(s) by which dopamine activated this important second messenger system was/were unknown. Although we showed that activation of the D5 dopamine receptor increased calcium concentrations, the restricted anatomic distribution of this receptor made this unlikely to be the major mechanism in brain. We have identified novel heteromeric dopamine receptor complexes that are linked to calcium signaling. The calcium pathway activated through the D1-D2 receptor heteromer involved coupl...
Source: Current Opinion in Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Hasbi A, O'Dowd BF, George SR Tags: Curr Opin Pharmacol Source Type: journals

Calcium-mediated modulation of the quaternary structure and function of adenosine A(2A)-dopamine D(2) receptor heteromers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The adenosine A(2A)-dopamine D(2) receptor heteromer is one of the most studied receptor heteromers. It has important implications for basal ganglia function and pathology. Recent studies using Bioluminescence and Sequential Resonance Energy Transfer techniques shed light on the role of Ca(2+) in the modulation of the quaternary structure of the A(2A)-D(2) receptor heteromer, which was found to depend on the binding of calmodulin (CaM) to the carboxy-terminus of the A(2A) receptor in the A(2A)-D(2) receptor heteromer. Importantly, the changes in quaternary structure correlate with changes in function. A Ca(2+)/CaM-depe...
Source: Current Opinion in Pharmacology - November 5, 2009 Category: Drugs & Pharmacology Authors: Ferré S, Woods AS, Navarro G, Aymerich M, Lluís C, Franco R Tags: Curr Opin Pharmacol Source Type: journals

Past, present and future of vasopressin and oxytocin receptor oligomers, prototypical GPCR models to study dimerization processes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The G protein-coupled receptors (GPCRs) play a major role in the regulation of physiological function. The emergence of the concept of GPCR oligomerization deeply modifies our understanding of their functioning. Much more than a simple association leading to an independent functioning, the GPCR oligomerization affects various steps such as membrane targeting of the receptors, binding of ligands, coupling to the intracellular pathways and internalization. Although significant advances have been performed in proving the existence of GPCR oligomers, its physiological impact remains to be established. Vasopressin and oxyto...
Source: Current Opinion in Pharmacology - November 5, 2009 Category: Drugs & Pharmacology Authors: Cottet M, Albizu L, Perkovska S, Jean-Alphonse F, Rahmeh R, Orcel H, Méjean C, Granier S, Mendre C, Mouillac B, Durroux T Tags: Curr Opin Pharmacol Source Type: journals

Emerging topics in type 2 diabetes: new mechanisms leading to new treatments?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19896899 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - November 5, 2009 Category: Drugs & Pharmacology Authors: Seedorf K, Ferré P Tags: Curr Opin Pharmacol Source Type: journals

Dopamine D(2)-D(3) receptor heteromers: pharmacological properties and therapeutic significance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Heteromerization of dopamine receptors has been shown for both the D(1)/D(5) and D(2)/D(3)/D(4) receptor families, which couple positively and negatively, respectively, to adenylyl cyclase. The present article reviews data on dopamine heteromers formed by D(3), focusing in particular on associations with their D(2) counterparts. Certain antiparkinsonian agents, like the preferential and high efficacy D(3)>D(2) agonists, pramipexole, and ropinirole, show amplified potency at D(2)-D(3) heteromers versus constituent monomers. Accordingly, in cells cotransfected with D(2) and D(3) receptors, pramipexole, and ropinirole ...
Source: Current Opinion in Pharmacology - November 5, 2009 Category: Drugs & Pharmacology Authors: Maggio R, Millan MJ Tags: Curr Opin Pharmacol Source Type: journals

CNS-targets in control of energy and glucose homeostasis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants w...
Source: Current Opinion in Pharmacology - October 31, 2009 Category: Drugs & Pharmacology Authors: Kleinridders A, Könner AC, Brüning JC Tags: Curr Opin Pharmacol Source Type: journals

Cannabinoid-opioid interactions during neuropathic pain and analgesia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Opiates and exogenous cannabinoids, both potent analgesics used for the treatment of patients with neuropathic pain, bind to and activate class A G-protein-coupled receptors (GPCRs). Several lines of evidence have recently suggested that opioid and cannabinoid receptors can functionally interact in the central nervous system (CNS). These interactions may be direct, such as through receptor heteromerization, or indirect, such as through signaling cross-talk that includes agonist-mediated release and/or synthesis of endogenous ligands that can activate downstream receptors. Interactions between opioid and cannabinoid rec...
Source: Current Opinion in Pharmacology - October 24, 2009 Category: Drugs & Pharmacology Authors: Bushlin I, Rozenfeld R, Devi LA Tags: Curr Opin Pharmacol Source Type: journals

New insights into mechanisms of gastrointestinal inflammation and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19857997 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - October 24, 2009 Category: Drugs & Pharmacology Authors: Ward SG, Mrsny R Tags: Curr Opin Pharmacol Source Type: journals

The role of neutrophils in the event of intestinal inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transmigration of polymorphonuclear leukocytes (PMNs; neutrophils) into the intestinal lumen is a classical phenomenon associated with a wide variety of disease states, including those of both pathogenic and autoimmune/idiopathic origin. While PMNs are highly effective at killing invading pathogens by releasing microbiocidal products, excessive or unnecessary release of these substances can cause substantial damage to the intestinal epithelium. Therefore, it is necessary to understand the underlying mechanisms that lure neutrophils into the lumen allowing them to perform their desired functions, so that researchers...
Source: Current Opinion in Pharmacology - October 23, 2009 Category: Drugs & Pharmacology Authors: Mumy KL, McCormick BA Tags: Curr Opin Pharmacol Source Type: journals

The role of dimerisation in the cellular trafficking of G-protein-coupled receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The concept that G-protein-coupled receptors can exist as homomeric and/or heteromeric complexes is now well established. Despite this, how dynamic such interactions are and if this may be modulated during receptor trafficking remain topics of debate. Use of endoplasmic reticulum trapping strategies and the generation of asymmetric homomers have started to provide information on the contribution of protein-protein interactions to receptor maturation, cell surface delivery and ligand-mediated endocytosis. Although dimer/oligomer formation appears to be essential for cell surface delivery of class A and class C GPCRs, th...
Source: Current Opinion in Pharmacology - October 20, 2009 Category: Drugs & Pharmacology Authors: Milligan G Tags: Curr Opin Pharmacol Source Type: journals

Opioid-receptor-heteromer-specific trafficking and pharmacology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Homomerization and heteromerization of 7 transmembrane spanning (7TM)/G-protein-coupled receptors (GPCRs) have been an important field of study. Whereas initial studies were performed in artificial cell systems, recent publications are shifting the focus to the in vivo relevance of heteromerization. This is especially apparent for the field of opioid receptors. Drugs have been identified that selectively target opioid heteromers of the delta-opioid receptor with the kappa and the mu-opioid receptors that influence nociception and ethanol consumption, respectively. In addition, in several cases, the specific physiologic...
Source: Current Opinion in Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: van Rijn RM, Whistler JL, Waldhoer M Tags: Curr Opin Pharmacol Source Type: journals

Dimerization of dopamine D1 and D3 receptors in the regulation of striatal function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Co-localization of dopamine D1 (D1R) and D3 receptors (D3R) in specific neuronal populations in the striatum and nucleus accumbens suggests that their cross-talk in the regulation of rewarding mechanisms and emotional and cognitive processes and in the development of motor dysfunctions might involve direct interactions. This paper summarizes recent data showing that D1R and D3R form a receptor heteromer in the striatum. A unique characteristic of this receptor complex is a synergistic interaction by which D3R stimulation increases D1R agonist affinity, allows a stronger stimulatory coupling of the D1R to the cAMP syste...
Source: Current Opinion in Pharmacology - October 15, 2009 Category: Drugs & Pharmacology Authors: Fiorentini C, Busi C, Spano P, Missale C Tags: Curr Opin Pharmacol Source Type: journals

How does inflammation cause Barrett's metaplasia?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Oesophageal adenocarcinoma conveys a poor prognosis and has a rapidly increasing incidence. Similarly, Barrett's metaplasia (a precursor lesion for oesophageal adenocarcinoma) has an increasing incidence. Both oesophageal adenocarcinoma and Barrett's metaplasia are more common in the context of inflammation as a result of acid and bile reflux. The cytokine profile of Barrett's metaplasia is predominantly a T-helper 2 response that contrasts with the T-helper 1 response in normal and inflamed oesophagus and normal intestine. A key transcription factor in the development of Barrett's metaplasia, CDX2, has recently been s...
Source: Current Opinion in Pharmacology - October 11, 2009 Category: Drugs & Pharmacology Authors: Colleypriest BJ, Ward SG, Tosh D Tags: Curr Opin Pharmacol Source Type: journals

Pathogen recognition receptors, cancer and inflammation in the gut.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pathogen recognition receptors (PRRs) initiate immediate responses against infection and tissue damage to protect the host from microbial invasion. In response to mucosal damage, intestinal PRR signaling initiates damage repair processes. Recent advances appear to link PRR abnormalities and inflammatory as well as neoplastic intestinal disorders. Emerging evidence suggests a dual role of PRRs, in which they may simultaneously induce tumorigenesis and antitumor immunity. PRR may induce tumor cell proliferation by activating cell survival signaling mainly via NF-kappaB, but this signal can activate dendritic cells to...
Source: Current Opinion in Pharmacology - October 11, 2009 Category: Drugs & Pharmacology Authors: Fukata M, Abreu MT Tags: Curr Opin Pharmacol Source Type: journals

Chemokine receptor oligomerization: functional considerations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins, trigger a broad array of biological responses ranging from cell polarization, movement, immune and inflammatory responses to prevention of HIV-1 infection. Chemokine-mediated cell activation was thought to be due to the binding of a monomeric chemokine to its monomeric receptor. Chemokine biology is nonetheless more complex than was initially predicted, as several studies suggest that chemokines can dimerize and that their receptors are found as dimers and/or higher order o...
Source: Current Opinion in Pharmacology - October 11, 2009 Category: Drugs & Pharmacology Authors: Thelen M, Muñoz LM, Rodríguez-Frade JM, Mellado M Tags: Curr Opin Pharmacol Source Type: journals

A role for the gut-to-brain GLP-1-dependent axis in the control of metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the past years tremendous amounts of clinical and fundamental data have been generated about GLP-1 and related therapeutic strategies for the treatment of type 2 diabetes. However, the cellular and physiological mechanisms through which GLP-1 is secreted, controls glycemia, and behaves as a therapeutic agent are certainly unclear. This is due to the dogma that proposes that upon glucose absorption GLP-1 is secreted into the hepatoportal blood flow, binds to its receptor at the surface of the insulin secreting beta cells, and triggers the secretion of insulin to control glycemia. However, these events have never be...
Source: Current Opinion in Pharmacology - September 29, 2009 Category: Drugs & Pharmacology Authors: Burcelin R, Serino M, Cabou C Tags: Curr Opin Pharmacol Source Type: journals

The role of mitochondria in health and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondria play a key role in energy metabolism in many tissues, including skeletal muscle and liver. Inherent disorders of mitochondria such as DNA deletions cause major disruption of metabolism and can result in severe impairment or death. However, the occurrence of such disorders is extremely rare and cannot account for the majority of metabolic disease. Recently, mitochondrial dysfunction of a more subtle nature in skeletal muscle has been implicated in the pathology of chronic metabolic disease characterized by insulin resistance such as obesity, type 2 diabetes mellitus, and aging. This hypothesis has been subs...
Source: Current Opinion in Pharmacology - September 28, 2009 Category: Drugs & Pharmacology Authors: Johannsen DL, Ravussin E Tags: Curr Opin Pharmacol Source Type: journals

Novel trends in high-throughput screening.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
High-throughput screening (HTS) is a well-established process for lead discovery in Pharma and Biotech companies and is now also being used for basic and applied research in academia. It comprises the screening of large chemical libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis. Since its first advent in the early to mid 1990s, the field of HTS has seen not only a continuous change in technology and processes, but also an adaptation to various needs in lead discovery. HTS has now evolved into a mature discipline that is a crucial source of che...
Source: Current Opinion in Pharmacology - September 20, 2009 Category: Drugs & Pharmacology Authors: Mayr LM, Bojanic D Tags: Curr Opin Pharmacol Source Type: journals

MicroRNAs in Barrett's esophagus and esophageal adenocarcinoma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The molecular genetics of Barrett's esophagus (BE) and its evolution to esophageal adenocarcinoma (EAC) have been widely studied; however, the molecular mechanism of BE-EAC carcinogenesis has not been completely understood. MicroRNA (miRNA) is now essential to understand the molecular mechanism of cancer progression. Recent findings include the following: firstly, miRNA expression profiles can distinguish between BE and EAC; secondly, miR-196a is upregulated in EAC tissues targeting annexin A1, thereby exerting antiapoptotic effects and contributing to EAC cell survival; miR-196a may also constitute a good biomarker of...
Source: Current Opinion in Pharmacology - September 18, 2009 Category: Drugs & Pharmacology Authors: Kan T, Meltzer SJ Tags: Curr Opin Pharmacol Source Type: journals

Reactive species and diabetes: counteracting oxidative stress to improve health.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Oxidative stress is at the very core of metabolism. Reactive species behave as true second messengers that control important cellular functions. However, under pathological conditions, abnormally large concentrations of these species may lead to permanent changes in signal transduction and gene expression. Attenuation of oxidative stress as a way to improve several diseases such as diabetes has flourished as one of the main challenges of research. The lack of evidence to prove the benefits from antioxidant compounds has led to boost these strategies. Inhibition of reactive oxygen species (ROS) production through the de...
Source: Current Opinion in Pharmacology - September 16, 2009 Category: Drugs & Pharmacology Authors: Pérez-Matute P, Zulet MA, Martínez JA Tags: Curr Opin Pharmacol Source Type: journals

Key pathogens and emerging therapies in infectious diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19766536 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - September 16, 2009 Category: Drugs & Pharmacology Authors: Miller PF, Mueller JP Tags: Curr Opin Pharmacol Source Type: journals

Stress hormones: physiological stress and regulation of metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Stress, defined as a state of threatened homeostasis, mobilizes a complex spectrum of adaptive physiologic and behavioral responses that aim to re-establish the challenged body homeostasis. The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) constitute the main effector pathways of the stress system, mediating its adaptive functions. In western societies, indices of stress correlate with increasing rates of both obesity and metabolic syndrome which have reached epidemic proportions. Recent data indicate that chronic stress, associated with mild hypercortisolemia and prolonged SNS acti...
Source: Current Opinion in Pharmacology - September 13, 2009 Category: Drugs & Pharmacology Authors: Kyrou I, Tsigos C Tags: Curr Opin Pharmacol Source Type: journals

Prospects for the next anti-Pseudomonas drug.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pseudomonas aeruginosa is one of the most dreaded Gram-negative bacterial pathogens in hospitals. Not only it is among the most frequently isolated Gram-negative organisms in bloodstream and wound infections, pneumonia, intra-abdominal-sepsis and urogenital-sepsis, but also it is frequently found in patients with comorbid illnesses and compromised by in-dwelling catheters, tubes and surgery where mortality rates of more than 60% have been reported. Besides its intrinsic resistance to a number of widely used antibiotics, Pseudomonas also managed to acquire resistance via additional mechanisms, including target mutations...
Source: Current Opinion in Pharmacology - September 10, 2009 Category: Drugs & Pharmacology Authors: Page MG, Heim J Tags: Curr Opin Pharmacol Source Type: journals

The role of chemokines in intestinal inflammation and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chronic inflammation is a risk factor for several gastrointestinal malignancies, including colorectal cancer. Recent epidemiological studies and clinical trials demonstrate that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) markedly reduced the relative risk of colorectal cancer. Chronic inflammation associated with development of cancer is partly driven by the chemokine system. Chemokines are chemoattractant cytokines that recruit leukocytes from the circulatory system to local inflammatory sites. In this review, we highlight recent breakthroughs in our understanding of the role of chemokines in infl...
Source: Current Opinion in Pharmacology - September 3, 2009 Category: Drugs & Pharmacology Authors: Wang D, Dubois RN, Richmond A Tags: Curr Opin Pharmacol Source Type: journals

New approaches in peptide antibiotics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The emergence and rapid spread of extremely multiresistant bacteria necessitates every effort to develop novel antibacterial agents. Host-derived antimicrobial peptides (AMPs) pexiganan (a magainin), omiganan (an indolicidin), and iseganan (a protegrin) have been in clinical phases for more than 10 years and provide little in combating against those bacteria. Even though some recent approaches may yield more effective and better-tolerated derivatives of host-derived AMPs, most novel derivatives suffer from weak activity, nonspecific cytotoxicity, and apparent susceptibility to proteolysis. Few have undergone any system...
Source: Current Opinion in Pharmacology - September 3, 2009 Category: Drugs & Pharmacology Authors: Vaara M Tags: Curr Opin Pharmacol Source Type: journals

Anti-Staphylococcus aureus immunotherapy: current status and prospects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Immunological prophylaxis and therapy for Staphylococcus aureus are attractive goals. However, there is nothing currently available in the clinic. Several approaches have failed and more are being undertaken. Here we assess current progress and the potential for success. PMID: 19733119 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - September 1, 2009 Category: Drugs & Pharmacology Authors: García-Lara J, Foster SJ Tags: Curr Opin Pharmacol Source Type: journals

Novel immunotherapeutic approaches to the treatment of infections caused by Gram-negative bacteria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The rise in infections caused by Gram-negative bacteria and the spread of resistance to conventional antibiotics provide significant challenges to the pharmaceutical industry. Monoclonal antibodies have achieved impressive recent clinical successes in a variety of indications, but to date there are no licensed immunotherapeutics that target bacterial infections, despite several promising studies in animal models of infection. Several key questions remain, in particular relating to the target(s), mechanism of action, and mode of delivery of any potential novel immunotherapeutic. This short review discusses recent approa...
Source: Current Opinion in Pharmacology - August 30, 2009 Category: Drugs & Pharmacology Authors: Palliyil S, Broadbent ID Tags: Curr Opin Pharmacol Source Type: journals

An update on community-associated MRSA virulence.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Staphylococcus aureus is a major health problem worldwide and the leading cause of bacterial infections in the United States. Historically, the success of S. aureus as a human pathogen has been facilitated by a strong propensity to develop antibiotic resistance and multidrug resistant strains are endemic in hospitals. However, one of the most striking developments in recent bacterial infectious disease history was the rapid emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). First reported in the 1990s, CA-MRSA has since emerged worldwide and is epidemic in the United States. The pathogen is ch...
Source: Current Opinion in Pharmacology - August 30, 2009 Category: Drugs & Pharmacology Authors: Kobayashi SD, Deleo FR Tags: Curr Opin Pharmacol Source Type: journals

Progress and new fields in molecular pharmacology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19726229 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - August 30, 2009 Category: Drugs & Pharmacology Authors: Boutin JA Tags: Curr Opin Pharmacol Source Type: journals

Aptamers: a new class of oligonucleotides in the drug discovery pipeline?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Aptamers are oligonucleotides identified in a randomly synthesized library containing up to 10(15) different molecules that fold into defined three-dimensional structures. Following their selection for predetermined properties at the end of an iterative process known as SELEX (Systematic Evolution of Ligands by Exponential enrichment) they can be chemically modified in order to provide them with additional properties. These molecules display both high affinity and specificity for their target. Aptamers constitute promising molecules for therapeutic applications as exemplified by pegaptanib, an aptamer-derived anti-VEGF...
Source: Current Opinion in Pharmacology - August 27, 2009 Category: Drugs & Pharmacology Authors: Dausse E, Da Rocha Gomes S, Toulmé JJ Tags: Curr Opin Pharmacol Source Type: journals

FGFs and metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although the first fibroblast growth factor (FGF) was discovered as a mitogen on 3T3 fibroblasts [Gospodarowicz D: Localization of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature 1974, 249:123-127], this name is functionally misleading. This group of secreted proteins consisting now of 22 members was composed based on common structural characteristics rather than on functional similarity. Thus, only a few members of the human FGF family promote growth and strictly act on fibroblasts. While the research in the last century firmly established FGFs as key players in devel...
Source: Current Opinion in Pharmacology - August 13, 2009 Category: Drugs & Pharmacology Authors: Kharitonenkov A Tags: Curr Opin Pharmacol Source Type: journals

Image-free assessment of protein translocation in live cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Protein translocation is a universal event shared by most cell signalling pathways to transmit signals between cell compartments. In recent years, the use of new fluorescence microscopy technologies combined with fluorescent probes-most often fluorescent proteins-and image analysis software has allowed the visualization and extensive analysis of such dynamic events in the context of the living cell. This review article focuses on emerging fluorescence approaches that tackle live cell protein translocation in the image-free context. Such methods are based on either protein-protein interactions or analysis of spatial dif...
Source: Current Opinion in Pharmacology - August 12, 2009 Category: Drugs & Pharmacology Authors: Furger C, Derick S, Boutin JA, Nosjean O Tags: Curr Opin Pharmacol Source Type: journals

Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Insulin receptor substrates (IRS) serine phosphorylation is a time-controlled physiological feedback mechanism in insulin signaling that is hijacked by metabolic and inflammatory stresses to promote insulin resistance. Kinases, including IKKbeta, JNK, ERK, mTOR, and S6K, activated by the inducers of insulin resistance induce uncontrolled IRS serine phosphorylation. Studies with genetically modified mice reveal that these kinases integrate signals from metabolic and inflammatory stresses in adipose tissue, liver, and hypothalamus leading to peripheral and central insulin resistance. Moreover, IKKbeta/NF-kappaB and JNK1 ...
Source: Current Opinion in Pharmacology - August 12, 2009 Category: Drugs & Pharmacology Authors: Tanti JF, Jager J Tags: Curr Opin Pharmacol Source Type: journals

Novel cytokine-targeted therapies and intestinal inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Several cytokines have been identified as critical mediators of chronic inflammation in inflammatory bowel disease (IBD) and biological therapies that target these molecules have been developed during recent years. Thereby, anti-TNF agents have noticeably improved the treatment of patients with IBD in comparison to conventional therapy. Furthermore, initial clinical trials showed promising results with anti-IL-6 and anti-IL-12/IL-23 agents. In addition to these well-known mediators of IBD, various novel cytokines have been described as critical during the pathogenesis of IBD in recent experimental studies and therapeut...
Source: Current Opinion in Pharmacology - August 9, 2009 Category: Drugs & Pharmacology Authors: Waldner MJ, Neurath MF Tags: Curr Opin Pharmacol Source Type: journals

Inflammation, a silent killer in cancer is not so silent!Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19671496 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - August 8, 2009 Category: Drugs & Pharmacology Authors: Aggarwal BB Tags: Curr Opin Pharmacol Source Type: journals

7TM pharmacology measured by label-free: a holistic approach to cell signalling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article will focus on key 7TM areas of interest where label-free has been particularly impactful of late rather than covering the principles behind the methodologies (which have been reviewed elsewhere). Firstly, it has facilitated the detection of endogenous or native-like cellular systems that are possibly more physiologically relevant; secondly, it has offered unprecedented angles to the probing of functional selectivity and ligand efficacy. PMID: 19671497 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - August 8, 2009 Category: Drugs & Pharmacology Authors: Rocheville M, Jerman JC Tags: Curr Opin Pharmacol Source Type: journals

Endoplasmic reticulum stress in beta-cells and development of diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The endoplasmic reticulum (ER) is a cellular compartment responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. A myriad of pathological and physiological factors perturb ER function and cause dysregulation of ER homeostasis, leading to ER stress. ER stress elicits a signaling cascade to mitigate stress, the unfolded protein response (UPR). As long as the UPR can relieve stress, cells can produce the proper amount of proteins and maintain ER homeostasis. If the UPR, however, fails to maintain ER homeostasis, cel...
Source: Current Opinion in Pharmacology - August 5, 2009 Category: Drugs & Pharmacology Authors: Fonseca SG, Burcin M, Gromada J, Urano F Tags: Curr Opin Pharmacol Source Type: journals

Inflammation and cancer: how friendly is the relationship for cancer patients?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present evidence that inhibitors of inflammatory biomarkers may have a role in both prevention and treatment of cancer. PMID: 19665429 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - August 5, 2009 Category: Drugs & Pharmacology Authors: Aggarwal BB, Gehlot P Tags: Curr Opin Pharmacol Source Type: journals

Neuroinflammation in Alzheimer's disease: different molecular targets and potential therapeutic agents including curcumin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly. Deposition of amyloid beta plaque and associated neuroinflammation are the major hallmarks of AD. Whereas reactive oxygen species (ROS) and activated microglial cells contribute to neuronal loss, nuclear factor kappaB and apolipoprotein E participate in inflammatory process of AD. Current FDA approved drugs provide only symptomatic relief in AD. For broad spectrum of activity, some natural products are also being tested. Turmeric is used as an anti-inflammatory medicine in various regions of Asia. Curcumin, which is a yellow colored polyphenol com...
Source: Current Opinion in Pharmacology - August 2, 2009 Category: Drugs & Pharmacology Authors: Ray B, Lahiri DK Tags: Curr Opin Pharmacol Source Type: journals

Regulation of proliferation, apoptosis and cell cycle in gastrointestinal disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Carcinogenesis is a multifactorial process representing the accumulation of acquired and genetic defects, and it has become apparent that many gastrointestinal cancers originate from a state of chronic inflammation. Advances in the field of inflammation-induced carcinogenesis over the past several years have focused on the creation of agonists or antagonists of cytokines and pathways regulating proliferation and apoptosis, and include advances such as the discovery of pharmacological inhibitors of the histone deacetylase (HDAC) family of transcriptional co-repressors, which induce apoptosis of neoplastic cells; discove...
Source: Current Opinion in Pharmacology - July 29, 2009 Category: Drugs & Pharmacology Authors: Jackson LN, Evers BM Tags: Curr Opin Pharmacol Source Type: journals

In vivo target validation using gene invalidation, RNA interference and protein functional knockout models: it is the time to combine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most diseases have multifactorial origins and their study requires complex in vivo validation strategies selected for their particular relevance. Most of the in vivo models used to date have been selected according to their availability and the accessibility of the corresponding technology platform. With the rapid development of new technologies, an increasing number of relevant systems for in vivo target validation are now available. In this review, we present in vivo loss-of-function tools acting at three biological levels (the gene, the messenger RNA and the protein); we discuss the specificity of each strategy and ...
Source: Current Opinion in Pharmacology - July 28, 2009 Category: Drugs & Pharmacology Authors: Vidalin O, Muslmani M, Estienne C, Echchakir H, Abina AM Tags: Curr Opin Pharmacol Source Type: journals

Carbon monoxide is a poison ... to microbes! CO as a bactericidal molecule.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Inflammation and immunity result in a wide range of disease processes, including chronic obstructive pulmonary disease, ischemia-reperfusion injury, atherosclerosis, vascular thrombosis and sepsis. Heme oxygenase-1 (HO-1) is a key enzyme that is indispensable for the temporal and spatial regulation of host response and, together with its essential metabolite carbon monoxide (CO), is crucial for maintaining homeostasis, inhibition of inflammation and the preservation of function and life. The biology of HO-1 is being discussed in this review series by Soares and colleagues and thus will not be reviewed here. Rather we w...
Source: Current Opinion in Pharmacology - July 26, 2009 Category: Drugs & Pharmacology Authors: Chin BY, Otterbein LE Tags: Curr Opin Pharmacol Source Type: journals

The tight junction in inflammatory disease: communication breakdown.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The intestinal epithelium restricts free passage of toxic and infectious molecules from the gut lumen while allowing selective paracellular absorption across the tight junction. Inflammatory bowel disease (IBD) patients demonstrate a loss of tight junction barrier function, increased pro-inflammatory cytokine production, and immune dysregulation; however, the relationship between these events is incompletely understood. Although tight junction barrier defects are insufficient to cause experimental IBD, mucosal immune activation is altered in response to increased epithelial permeability. Thus, an evolving model suggest...
Source: Current Opinion in Pharmacology - July 23, 2009 Category: Drugs & Pharmacology Authors: Edelblum KL, Turner JR Tags: Curr Opin Pharmacol Source Type: journals

Extracellular nucleotides as negative modulators of immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nucleotides are well known for being the universal currency of intracellular energy transactions, but over the past decade it has become clear that they are also ubiquitous extracellular messengers. In the immune system there is increasing awareness that nucleotides serve multiple roles as stimulants of lymphocyte proliferation, ROS generation, cytokine and chemokine secretion: in one word as pro-inflammatory mediators. However, although often neglected, extracellular nucleotides exert an additional more subtle function as negative modulators of immunity, or as immunedepressants. The more we understand the peculiar bio...
Source: Current Opinion in Pharmacology - July 20, 2009 Category: Drugs & Pharmacology Authors: Di Virgilio F, Boeynaems JM, Robson SC Tags: Curr Opin Pharmacol Source Type: journals

Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Obesity and associated metabolic disorders are worldwide epidemic. The literature provides new evidence that gut microbiota dysbiosis (at the phyla, genus, or species level) affects host metabolism and energy storage. Here we discuss new findings that may explain how gut microbiota can be involved in the development or in the control of obesity and associated low-grade inflammation. New powerful molecular biology methods and the use of gnotobiotic animal allowed to analyze the molecular link between gut bacteria and the host. Moreover, even if more studies are needed to unravel how changing gut microbiota impacts on th...
Source: Current Opinion in Pharmacology - July 20, 2009 Category: Drugs & Pharmacology Authors: Cani PD, Delzenne NM Tags: Curr Opin Pharmacol Source Type: journals

Airway irritability-a burning issue?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systems biology is being increasingly used to probe the underlying pathophysiology of asthma, although serious challenges remain to decipher the physiologic significance of the information revealed in these studies relating to gene expression and regulatory gene networks often used to understand gene-gene interactions. One phenotypic change characteristic of asthma is increased airway irritability, or bronchial hyperresponsiveness (BHR) which is still poorly understood. While the precise mechanism(s) remain(s) to be identified, a number of hypotheses have been posited to account for this phenomenon, including airways i...
Source: Current Opinion in Pharmacology - July 19, 2009 Category: Drugs & Pharmacology Authors: Spina D, Page C Tags: Curr Opin Pharmacol Source Type: journals

Identification of novel immunosuppressive pathways paves the way for drug discovery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19625216 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - July 19, 2009 Category: Drugs & Pharmacology Authors: Di Virgilio F, Robson SC Tags: Curr Opin Pharmacol Source Type: journals

Therapeutic targeting of myeloid-derived suppressor cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Myeloid-derived suppressor cells (MDSCs) represent a subset of myeloid cells that expand under pathological conditions, such as cancer development, acute and chronic infections, trauma, bone marrow transplantations, and some autoimmune diseases. MDSCs mediate a negative regulation of the immune response by affecting different T lymphocyte subsets. Potential mechanisms, which underlie this inhibitory activity range from those requiring direct cell-to-cell contact with others, more indirect, and mediated by the modification of the microenvironment. Pharmacological inhibition of MDSC suppressive pathways is a promising st...
Source: Current Opinion in Pharmacology - July 15, 2009 Category: Drugs & Pharmacology Authors: Ugel S, Delpozzo F, Desantis G, Papalini F, Simonato F, Sonda N, Zilio S, Bronte V Tags: Curr Opin Pharmacol Source Type: journals