Conotoxins As Tools to Understand the Physiological Function of Voltage-Gated Calcium (Cav) Channels
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Genetic Associations Between Voltage-Gated Calcium Channels (Vgccs) and Autism Spectrum Disorder (ASD)
Liao and Li Molecular Brain (2020) 13:96 https://doi.org/10.1186/s13041-020-00634-0 REVIEW Open Access Genetic associations between voltage- gated calcium channels and autism spectrum disorder: a systematic review Xiaoli Liao1,2 and Yamin Li2* Abstract Objectives: The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD). Methods: A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions. Results: From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACN A1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca2+ pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD. Conclusions: Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype. Keywords: Autism spectrum disorder, Voltage-gated calcium -
Interactions of Insecticidal Spider Peptide Neurotoxins with Insect Voltage- and Neurotransmitter-Gated Ion Channels
Interactions of insecticidal spider peptide neurotoxins with insect voltage- and neurotransmitter-gated ion channels (Molecular representation of - HXTX-Hv1c including key binding residues, adapted from Gunning et al, 2008) PhD Thesis Monique J. Windley UTS 2012 CERTIFICATE OF AUTHORSHIP/ORIGINALITY I certify that the work in this thesis has not previously been submitted for a degree nor has it been submitted as part of requirements for a degree except as fully acknowledged within the text. I also certify that the thesis has been written by me. Any help that I have received in my research work and the preparation of the thesis itself has been acknowledged. In addition, I certify that all information sources and literature used are indicated in the thesis. Monique J. Windley 2012 ii ACKNOWLEDGEMENTS There are many people who I would like to thank for contributions made towards the completion of this thesis. Firstly, I would like to thank my supervisor Prof. Graham Nicholson for his guidance and persistence throughout this project. I would like to acknowledge his invaluable advice, encouragement and his neverending determination to find a solution to any problem. He has been a valuable mentor and has contributed immensely to the success of this project. Next I would like to thank everyone at UTS who assisted in the advancement of this research. Firstly, I would like to acknowledge Phil Laurance for his assistance in the repair and modification of laboratory equipment. To all the laboratory and technical staff, particulary Harry Simpson and Stan Yiu for the restoration and sourcing of equipment - thankyou. I would like to thank Dr Mike Johnson for his continual assistance, advice and cheerful disposition. -
Could Mycolactone Inspire New Potent Analgesics? Perspectives and Pitfalls
toxins Review Could Mycolactone Inspire New Potent Analgesics? Perspectives and Pitfalls 1 2 3, 4, , Marie-Line Reynaert , Denis Dupoiron , Edouard Yeramian y, Laurent Marsollier * y and 1, , Priscille Brodin * y 1 France Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France 2 Institut de Cancérologie de l’Ouest Paul Papin, 15 rue André Boquel-49055 Angers, France 3 Unité de Microbiologie Structurale, Institut Pasteur, CNRS, Univ. Paris, F-75015 Paris, France 4 Equipe ATIP AVENIR, CRCINA, INSERM, Univ. Nantes, Univ. Angers, 4 rue Larrey, F-49933 Angers, France * Correspondence: [email protected] (L.M.); [email protected] (P.B.) These three authors contribute equally to this work. y Received: 29 June 2019; Accepted: 3 September 2019; Published: 4 September 2019 Abstract: Pain currently represents the most common symptom for which medical attention is sought by patients. The available treatments have limited effectiveness and significant side-effects. In addition, most often, the duration of analgesia is short. Today, the handling of pain remains a major challenge. One promising alternative for the discovery of novel potent analgesics is to take inspiration from Mother Nature; in this context, the detailed investigation of the intriguing analgesia implemented in Buruli ulcer, an infectious disease caused by the bacterium Mycobacterium ulcerans and characterized by painless ulcerative lesions, seems particularly promising. More precisely, in this disease, the painless skin ulcers are caused by mycolactone, a polyketide lactone exotoxin. In fact, mycolactone exerts a wide range of effects on the host, besides being responsible for analgesia, as it has been shown notably to modulate the immune response or to provoke apoptosis. -
CACNB1 Antibody (C-Term) Blocking Peptide Synthetic Peptide Catalog # Bp16144b
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 CACNB1 Antibody (C-term) Blocking Peptide Synthetic peptide Catalog # BP16144b Specification CACNB1 Antibody (C-term) Blocking CACNB1 Antibody (C-term) Blocking Peptide - Peptide - Background Product Information The protein encoded by this gene belongs to Primary Accession Q02641 the calciumchannel beta subunit family. It plays an important role in thecalcium channel by modulating G protein inhibition, increasing CACNB1 Antibody (C-term) Blocking Peptide - Additional Information peakcalcium current, controlling the alpha-1 subunit membrane targetingand shifting the voltage dependence of activation and Gene ID 782 inactivation.Alternative splicing occurs at this locus and three transcriptvariants encoding Other Names three distinct isoforms have been identified. Voltage-dependent L-type calcium channel subunit beta-1, CAB1, Calcium channel CACNB1 Antibody (C-term) Blocking voltage-dependent subunit beta 1, CACNB1, Peptide - References CACNLB1 Format Jangsangthong, W., et al. Pflugers Arch. Peptides are lyophilized in a solid powder 459(3):399-411(2010)Olsen, J.V., et al. Cell format. Peptides can be reconstituted in 127(3):635-648(2006)Olsen, J.V., et al. Cell solution using the appropriate buffer as 127(3):635-648(2006)Lim, J., et al. Cell needed. 125(4):801-814(2006)Foell, J.D., et al. Physiol. Genomics 17(2):183-200(2004) Storage Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C. Precautions This product is for -
Ketamine: an Update for Its Use in Complex Regional Pain Syndrome
xperim & E en l ta a l ic P in h Bentley et al., Clin Exp Pharmacol 2015, 5:2 l a C r m f Journal of DOI: 10.4172/2161-1459.1000169 o a l c a o n l o r g u y o J ISSN: 2161-1459 Clinical and Experimental Pharmacology Commentry Open Access Ketamine: An Update for Its Use in Complex Regional Pain Syndrome and Major Depressive Disorder William E Bentley*, Michael Sabia, Michael E Goldberg and Irving W Wainer Cooper University Hospital, Camden, New Jersey, United States of America Abstract In recent years, there has been significant research in regard to the efficacy of ketamine in regards to treating Complex Regional Pain Syndrome (CRPS) and Major Depressive Disorder (MDD). Many patients have had substantial symptomatic relief; however, not all patients have had positive results. This has prompted current research with evidence to suggest certain biomarkers exist that would infer which patients will/will not respond to ketamine treatment. Current biomarkers of interest include D-Serine (D-Ser) and magnesium, which will be discussed. Whether or not D-Ser and/or magnesium levels should be checked and possibly dictate therapy is an area of future research. It is also possible that downstream metabolites of ketamine are the key to successful therapy. Keywords: Complex regional pain syndrome; Major Depressive thoughts; and slowing of speech and action. These changes must last a Disorder(MDD); Ketamine minimum of 2 weeks and interfere considerably with work and family relations” [6]. Treatment options include antidepressant medications, Complex Regional Pain Syndrome (CRPS) and Major Depressive cognitive behavioral therapy, and interpersonal therapy. -
ACPA Guide to Pain Management
[Document title] [Document subtitle] Abstract [Draw your reader in with an engaging abstract. It is typically a short summary of the document. When you’re ready to add your content, just click here and start typing.] ACPA [Email address] 1 ACPA Resource Guide To Chronic Pain Management An Integrated Guide to Medical, Interventional, Behavioral, Pharmacologic and Rehabilitation Therapies 2019 Edition American Chronic Pain Association P.O. Box 850 Rocklin, CA 95677 Tel 800-533-3231 Fax 916-652-8190 E-mail [email protected] Web Site http://www.theacpa.org Copyright 2019 American Chronic Pain Association, Inc. All rights reserved. No portion of this book may be reproduced without permission of the American Chronic Pain Association, Inc. 2 Table of Contents A STATEMENT FROM THE ACPA BOARD OF DIRECTORS ...........................................................................................................................5 INTRODUCTION ........................................................................................................................................................................................................6 OVERVIEW OF CHRONIC PAIN TREATMENT ..................................................................................................................................................8 WHAT DOES SUCCESSFUL PAIN TREATMENT LOOK LIKE? .......................................................................................................................8 PAIN TYPES, SOURCES & CLASSIFICATION .....................................................................................................................................................9 -
An Integrated Genomic Analysis of Gene-Function Correlation on Schizophrenia Susceptibility Genes
Journal of Human Genetics (2010) 55, 285–292 & 2010 The Japan Society of Human Genetics All rights reserved 1434-5161/10 $32.00 www.nature.com/jhg ORIGINAL ARTICLE An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes Tearina T Chu and Ying Liu Schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665–75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia. -
Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review
Current Pain and Headache Reports (2019) 23: 37 https://doi.org/10.1007/s11916-019-0774-0 OTHER PAIN (A KAYE AND N VADIVELU, SECTION EDITORS) Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review Omar Viswanath1,2,3 & Ivan Urits4 & Mark R. Jones4 & Jacqueline M. Peck5 & Justin Kochanski6 & Morgan Hasegawa6 & Best Anyama7 & Alan D. Kaye7 Published online: 1 May 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review Neuropathic pain is often debilitating, severely limiting the daily lives of patients who are affected. Typically, neuropathic pain is difficult to manage and, as a result, leads to progression into a chronic condition that is, in many instances, refractory to medical management. Recent Findings Gabapentinoids, belonging to the calcium channel blocking class of drugs, have shown good efficacy in the management of chronic pain and are thus commonly utilized as first-line therapy. Various sodium channel blocking drugs, belonging to the categories of anticonvulsants and local anesthetics, have demonstrated varying degrees of efficacy in the in the treatment of neurogenic pain. Summary Though there is limited medical literature as to efficacy of any one drug, individualized multimodal therapy can provide significant analgesia to patients with chronic neuropathic pain. Keywords Neuropathic pain . Chronic pain . Ion Channel blockers . Anticonvulsants . Membrane stabilizers Introduction Neuropathic pain, which is a result of nervous system injury or lives of patients who are affected. Frequently, it is difficult to dysfunction, is often debilitating, severely limiting the daily manage and as a result leads to the progression of a chronic condition that is, in many instances, refractory to medical This article is part of the Topical Collection on Other Pain management. -
Slow Inactivation in Voltage Gated Potassium Channels Is Insensitive to the Binding of Pore Occluding Peptide Toxins
Biophysical Journal Volume 89 August 2005 1009–1019 1009 Slow Inactivation in Voltage Gated Potassium Channels Is Insensitive to the Binding of Pore Occluding Peptide Toxins Carolina Oliva, Vivian Gonza´lez, and David Naranjo Centro de Neurociencias de Valparaı´so, Facultad de Ciencias, Universidad de Valparaı´so, Valparaı´so, Chile ABSTRACT Voltage gated potassium channels open and inactivate in response to changes of the voltage across the membrane. After removal of the fast N-type inactivation, voltage gated Shaker K-channels (Shaker-IR) are still able to inactivate through a poorly understood closure of the ion conduction pore. This, usually slower, inactivation shares with binding of pore occluding peptide toxin two important features: i), both are sensitive to the occupancy of the pore by permeant ions or tetraethylammonium, and ii), both are critically affected by point mutations in the external vestibule. Thus, mutual interference between these two processes is expected. To explore the extent of the conformational change involved in Shaker slow inactivation, we estimated the energetic impact of such interference. We used kÿconotoxin-PVIIA (kÿPVIIA) and charybdotoxin (CTX) peptides that occlude the pore of Shaker K-channels with a simple 1:1 stoichiometry and with kinetics 100-fold faster than that of slow inactivation. Because inactivation appears functionally different between outside-out patches and whole oocytes, we also compared the toxin effect on inactivation with these two techniques. Surprisingly, the rate of macroscopic inactivation and the rate of recovery, regardless of the technique used, were toxin insensitive. We also found that the fraction of inactivated channels at equilibrium remained unchanged at saturating kÿPVIIA. -
Modifications to the Harmonized Tariff Schedule of the United States To
U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b). -
Redalyc.Neurobiological Alterations in Alcohol Addiction: a Review
Adicciones ISSN: 0214-4840 [email protected] Sociedad Científica Española de Estudios sobre el Alcohol, el Alcoholismo y las otras Toxicomanías España Erdozain, Amaia M.; Callado, Luis F. Neurobiological alterations in alcohol addiction: a review Adicciones, vol. 26, núm. 4, octubre-diciembre, 2014, pp. 360-370 Sociedad Científica Española de Estudios sobre el Alcohol, el Alcoholismo y las otras Toxicomanías Palma de Mallorca, España Available in: http://www.redalyc.org/articulo.oa?id=289132934009 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative revisión adicciones vol. 26, nº 3 · 2014 Neurobiological alterations in alcohol addiction: a review Alteraciones neurobiológicas en el alcoholismo: revisión Amaia M. Erdozain*,*** and Luis F. Callado*,** *Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain. **Biocruces Health Research Institute, Bizkaia, Spain. ***Neuroscience Paris Seine, Université Pierre et Marie Curie, Paris, France Resumen Abstract Todavía se desconoce el mecanismo exacto mediante el cual el etanol The exact mechanism by which ethanol exerts its effects on the brain produce sus efectos en el cerebro. Sin embargo, hoy en día se sabe is still unknown. However, nowadays it is well known that ethanol que el etanol interactúa con proteínas específicas de la membrana interacts with specific neuronal membrane proteins involved in neuronal, implicadas en la transmisión de señales, produciendo así signal transmission, resulting in changes in neural activity. -
Mechanism-Specific Assay Design Facilitates the Discovery of Nav1.7
Mechanism-specific assay design facilitates the PNAS PLUS discovery of Nav1.7-selective inhibitors Tania Chernov-Rogana, Tianbo Lia, Gang Lua, Henry Verschoofb, Kuldip Khakhb, Steven W. Jonesa, Maureen H. Beresinia, Chang Liua, Daniel F. Ortwinec, Steven J. McKerrallc, David H. Hackosd, Daniel Sutherlinc, Charles J. Cohenb, and Jun Chena,1 aDepartment of Biochemical and Cellular Pharmacology, Genentech Inc., San Francisco, CA 94080; bXenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada; cDepartment of Chemistry, Genentech Inc., San Francisco, CA 94080; and dDepartment of Neuroscience, Genentech Inc., San Francisco, CA 94080 Edited by Bruce P. Bean, Harvard Medical School, Boston, MA, and approved December 11, 2017 (received for review August 30, 2017) Many ion channels, including Nav1.7, Cav1.3, and Kv1.3, are linked therefore are nonselective (14). Recently, a group of arylsulfo- to human pathologies and are important therapeutic targets. To namides was identified as selective Nav1.7 inhibitors (15, 16). develop efficacious and safe drugs, subtype-selective modulation These compounds were discovered empirically, before our cur- is essential, but has been extremely difficult to achieve. We rent understanding that they bind to the voltage-sensing domain postulate that this challenge is caused by the poor assay design, 4 (VSD4) instead of the central cavity. However, PF-771, the and investigate the Nav1.7 membrane potential assay, one of the most advanced compound, was recently halted from clinical most extensively employed screening assays in modern drug development, raising concerns about this chemical class. discovery. The assay uses veratridine to activate channels, and To identify subtype-selective chemical scaffolds, large libraries compounds are identified based on the inhibition of veratridine- of compounds, sometimes exceeding millions of individual evoked activities.