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Migraine is a chronic neurovascular disease that affects about 15% of the population and is characterized by recurrent episodes of unilateral throbbing headaches with associated symptoms such as nausea, vomiting, photophobia and phonophobia. For many patients, available pharmacological options do not meet their expectations, because of lake of efficacy, side effects for because they have contraindications. Lately, proof-of-concept clinical trials show that the blockade of CGRP receptors, a neuropeptide that is found in 50% of trigeminovascular neurones, can significantly decrease many migraine symptoms without inducing any vasoconstriction and that these molcules are beeing very well tolerated, even in patients with cardiovascular dieases. This leads to the development of many other molecules. None of them did pass the phase 2 of clinical trials but the Telcagepant. This molecule has been shown to be very efficient and well tolerated in the acute treatment of migraine. However, its development has been stopped because of hepatotoxicity concerns have been found out in trials about prophylactic use, but not in its acute use, maintaining absence of pharmacological options for the acute treatment of migraine for migrainers who also suffer from cardiovascular diseases. More recently, antibodies against CGRP or its receptors have been developped for the prophylactic management of migraine and seem to be very promising. The promising nature of all these molecules in the treatment of acute migraine attacks or in its prophylaxis will be discussed. La migraine est un désordre neuro-vasculaire présent chez environ 15% de la population et se manifeste par des épisodes récurrents de céphalées lancinantes hémilatérales associées à de nombreux autres symptômes, tels que nausées, vomissements, photophobie et/ou phonophobie. Pour de nombreux patients, les options pharmacologiques disponibles actuellement sur le marché pour le traitement de leurs crises de migraine ne répondent pas à leurs attentes, par manque d’efficacité, à cause d’effets secondaires mal supportés, ou car ceux-ci leur sont contre-indiqués. Dernièrement, des études « preuve de concept » ont montré que le blocage des récepteurs du CGRP, un neuropeptide présent dans 50% des neurones du système trigémino-vasculaire, diminuait significativement de nombreux symptômes de la crise de migraine sans induire de vasoconstriction et était très bien toléré, y compris chez les patients présentant des pathologies cardiovasculaires, ce qui a mené au développement de plusieurs petites molécules. De ces nombreuses petites molécules étant allées jusqu’en phase II, seul le Telcagepant a été testé en étude clinique de phase III. Celui-ci s’est avéré efficace et très bien toléré dans le traitement de crise de la migraine. Son développement a malheureusement été interrompu par la firme à cause de la détection d’une hépatotoxicité en usage quotidien dans un but prophylactique, maintenant l’absence d’options pharmacologiques de traitement de la migraine aiguë pour les patients migraineux et souffrant de pathologies cardiovasculaires. Plus récemment, des anticorps ciblant le CGRP ou les récepteurs du CGRP sont entrés en développement dans le traitement prophylactique de la migraine et s’avèrent très prometteurs. L’intérêt de toutes ces molécules et leur potentiel dans la prise en charge aiguë ou prophylactique de la migraine sera discuté dans ce mémoire.

Receptors, Calcitonin Gene-Related Peptide --- Migraine Disorders

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Human biochemistry --- Cardiovascular System. --- Nervous System. --- Nervous System --- Calcitonin gene-related peptide --- Gastrointestinal system --- Receptors, endogenous substances --- Urinary tract

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This book contains a comprehensive series of reviews on the calcitonin gene-related peptide (CGRP) family of peptides. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition. This volume includes chapters on: The adrenomedullin peptides and signalling Ligand binding and activation of the CGRP receptor Understanding amylin receptors The CGRP-receptor component protein The calcitonin peptide family Genetic regulation of CGRP Vascular actions of CGRP and adrenomedullin Intermedin/adrenomedullin 2 function CGRP and adrenomedullin as pain-related peptides Amylinergic control of ingestive behaviour Calcitonin receptors This book discusses their receptors, physiological and pathophysiological functions and potential as clinical targets. It will appeal to researchers who study any of these peptides and those with an interest in migraine therapy due to the involvement of CGRP in this disorder. The book is unique because it brings together research on the whole peptide family for the first time in several years. It will be a useful reference volume for researchers in this area. This book will also appeal to researchers in the broader field of bioactive peptides.

Calcitonin gene-related peptide. --- Calcitonin. --- Peptides. --- Calcitonin gene-related peptide --- Neuropeptides --- Biological Science Disciplines --- Calcitonin Gene-Related Peptide --- Physiology --- Nerve Tissue Proteins --- Peptides --- Natural Science Disciplines --- Disciplines and Occupations --- Amino Acids, Peptides, and Proteins --- Proteins --- Chemicals and Drugs --- Human Anatomy & Physiology --- Animal Biochemistry --- Health & Biological Sciences --- Neuropeptides. --- Brain peptides --- Medicine. --- Cancer research. --- Gene expression. --- Endocrinology. --- Biomedicine. --- Biomedicine general. --- Gene Expression. --- Cancer Research. --- Nerve tissue proteins --- Neurotransmitters --- Oncology. --- Tumors --- Genes --- Genetic regulation --- Internal medicine --- Hormones --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Expression --- Endocrinology . --- Biomedicine, general. --- Health Workforce --- Cancer research --- Medicine --- Biology --- Molecular genetics. --- Cancer. --- Biomedical Research. --- Molecular Genetics. --- Cancer Biology. --- Research. --- Cancers --- Carcinoma --- Malignancy (Cancer) --- Malignant tumors --- Genetics --- Molecular biology --- Biological research --- Biomedical research

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Almost 25 years ago, the first mammalian transient receptor potential (TRP) channel was cloned and published. TRP channels now represent an extended family of 28 members fulfilling multiple roles in the living organism. Identified functions include control of body temperature, transmitter release, mineral homeostasis, chemical sensing, and survival mechanisms in a challenging environment. The TRP channel superfamily covers six families: TRPC with C for “canonical”, TRPA with A for “ankyrin”, TRPM with M for “melastatin”, TRPML with ML for “mucolipidin”, TRPP with P for “polycystin”, and TRPV with V for “vanilloid”. Over the last few years, new findings on TRP channels have confirmed their exceptional function as cellular sensors and effectors. This Special Book features a collection of 8 reviews and 7 original articles published in “Cells” summarizing the current state-of-the-art on TRP channel research, with a main focus on TRP channel activation, their physiological and pathophysiological function, and their roles as pharmacological targets for future therapeutic options.

n/a --- transient receptor potential channels --- photochromic ligands --- elementary immunology --- Purkinje cell --- EPSC --- substance P --- chemicals --- organ toxicity --- lymphocytes --- HSP70 --- physiology --- bioavailable --- inflammatory bowel disease --- platelets --- pollutants --- yeast --- regulatory T cells --- kinase --- Saccharomyces cerevisiae --- manganese --- cerebellum --- TRP channel --- NHERF --- inflammation --- nanoHPLC-ESI MS/MS --- TRPM7 --- chemical probes --- TRPM8 --- dorsal column nuclei --- TRPV2 --- TRPV3 --- calcitonin gene-related peptide --- TRPV1 --- ion channels --- transient receptor potential --- 2D gel electrophoresis --- MALDI-TOF MS(/MS) --- TRPV4 --- overproduction --- sulfur mustard --- oxidative stress --- graft versus host disease --- menthol --- topical --- chemosensor --- AP18 --- calcium signalling --- mucosal epithelium --- cuneate nucleus --- production platform --- TRPC channels --- ulcerative colitis --- channel structure --- xerostomia --- neutrophils --- cardiovascular system --- TRPC5 --- TRPC6 --- TRPC3 --- TRPC4 --- calcium signaling --- protein purification --- adipose tissue --- transient receptor potential (TRP) channels --- sodium --- TH17 --- diacylglycerol --- hypersensitivity --- TRPY1 --- GABAB --- HEK293 --- thrombosis --- ion channel --- TRPC --- pathophysiology --- SMAD --- toxicology --- endothelium --- calcium --- proteomics --- TRPA1 --- salivary glands --- TRP channels --- lipid mediators --- sensors --- radiation --- TRPM4 channel --- human medulla oblongata --- mGluR1 --- small molecules --- TRPC3 pharmacology