神经系统疾病与TRP通道的关系

Y. Yazğan
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Examination of transient receptor potential (TRP) channels is at an early stage in the investigation of the molecular principle of these diseases, but clear results regarding the efficacy of substances activating or inhibiting these channels have not been obtained. Some diseases have been based on mutations of TRP channels. However, only a few TRP channelopathies, have been conclusively identified so far [1]. Investigation of TRP channels in psychiatric disorders will contribute to a better understanding of the etiology of psychiatric disorders and the development of new pharmacological treatments. Abbreviations: TRP: Transient Receptor Potential; GPCR: G Protein Coupled Receptor; TRPV1: TRP Vanilloid 1; CGRP: Calcitonin Gene Related Peptide; CNS: Central Nervous System; SOC: Store Operated Calcium Channels; BDNF: Brain Derived Neurotrophic Factor; Mwk: Moon Walker Mouse; BD-I: Bipolar Disorder Type I; ALS-G: Guamanian Amyotrophic Lateral Sclerosis ISSN: 2637-6628 DOI: 10.32474/OJNBD.2018.01.000120 On J Neur & Br Disord Copyrights@ Yener Yazğan. Citation: Yener Y, Betül Y. Neurological Diseases and Relation of TRP Channels. On J Neur & Br Disord 1(4)2018. OJNBD. MS.ID.000120. DOI: 10.32474/OJNBD.2018.01.000120. 71 TRP Channels in Brain Disorders TRPV1 and TRPA1 Significant evidence has been obtained that TRPV1 antagonists have anxiolytic activity in preclinical studies, but the antidepressant effect is not clear [6]. There is no direct evidence that TRP channels play a role in schizophrenia. 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引用次数: 0

摘要

目前被用作涵盖“大脑障碍”、神经系统疾病和精神障碍的综合定义。精神分裂症、抑郁症、恐慌症、毒瘾和失眠被称为“精神障碍”,癫痫、阿尔茨海默病、帕金森病、亨廷顿舞蹈症和多发性硬化症被视为“神经系统疾病”。目前治疗这些非常常见的疾病需要持续用药,同时会导致许多不同的副作用。因此,对新治疗方法的临床前和临床研究正在增加。尤其是这些疾病的分子基础的鉴定是研究的重点。瞬时受体电位(TRP)通道的检查处于研究这些疾病的分子原理的早期阶段,但尚未获得关于激活或抑制这些通道的物质功效的明确结果。一些疾病是基于TRP通道的突变。然而,到目前为止,只有少数TRP通道病被最终确定[1]。对精神障碍中TRP通道的研究将有助于更好地了解精神障碍的病因和开发新的药物治疗方法。缩写:TRP:瞬时受体电位;GPCR:G蛋白偶联受体;TRPV1:TRP香草1;降钙素基因相关肽;中枢神经系统;SOC:存储操作的钙通道;BDNF:脑源性神经营养因子;Mwk:月球漫步鼠;BD-I:I型双相情感障碍;ALS-G:Guamanian肌萎缩性侧索硬化症ISSN:2637-6268 DOI:10.32474/OJNBD.2018.01.000120 On J Neur&Br Disord Copyrights@Yener Yazğan。引文:Yener Y,Betül Y.神经系统疾病与TRP通道的关系。关于J Neur&Br Disord 1(4)2018。OJNBD。MS.ID.000120.DOI:10.32474/OJNBD.2011.01.000120。71脑疾病中的TRP通道TRPV1和TRPA1在临床前研究中已经获得了TRPV1拮抗剂具有抗焦虑活性的重要证据,但抗抑郁作用尚不清楚[6]。没有直接证据表明TRP通道在精神分裂症中起作用。然而,TRPV1通道在中枢多巴胺能和大麻素机制中发挥作用的事实可能表明这些通道在精神分裂症中的潜在作用[5]。CGRP从三叉神经血管系统神经元网络的释放和神经源性炎症反应是目前公认的偏头痛发作病理生理机制。特别地,TRP香草素1(TRPV1)和TRP锚蛋白1(TRPA1)在伤害性神经元中表达,伤害性神经元也表达感觉神经肽、速激肽和降钙素基因相关肽(CGRP),它们介导神经源性炎症反应。这一证据表明,这些通道可能是偏头痛治疗的一个重要治疗目标[7]。
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Neurological Diseases and Relation of TRP Channels
Is currently used as a comprehensive definition covering “brain disorders”, neurological diseases and mental disorders. While schizophrenia, depression, panic disorder, drug addiction and insomnia are referred to as “mental disorders”, Epilepsy, Alzheimer, Parkinson, Huntington’s disease (HD) and multiple sclerosis are considered as “neurological disorders”. Current therapies of these very common diseases require continuous drug use and at the same time cause many different side effects. Therefore preclinical and clinical investigations for new treatment approaches are on the rise. Especially the identification of the molecular basis of these diseases is the focus of researches. Examination of transient receptor potential (TRP) channels is at an early stage in the investigation of the molecular principle of these diseases, but clear results regarding the efficacy of substances activating or inhibiting these channels have not been obtained. Some diseases have been based on mutations of TRP channels. However, only a few TRP channelopathies, have been conclusively identified so far [1]. Investigation of TRP channels in psychiatric disorders will contribute to a better understanding of the etiology of psychiatric disorders and the development of new pharmacological treatments. Abbreviations: TRP: Transient Receptor Potential; GPCR: G Protein Coupled Receptor; TRPV1: TRP Vanilloid 1; CGRP: Calcitonin Gene Related Peptide; CNS: Central Nervous System; SOC: Store Operated Calcium Channels; BDNF: Brain Derived Neurotrophic Factor; Mwk: Moon Walker Mouse; BD-I: Bipolar Disorder Type I; ALS-G: Guamanian Amyotrophic Lateral Sclerosis ISSN: 2637-6628 DOI: 10.32474/OJNBD.2018.01.000120 On J Neur & Br Disord Copyrights@ Yener Yazğan. Citation: Yener Y, Betül Y. Neurological Diseases and Relation of TRP Channels. On J Neur & Br Disord 1(4)2018. OJNBD. MS.ID.000120. DOI: 10.32474/OJNBD.2018.01.000120. 71 TRP Channels in Brain Disorders TRPV1 and TRPA1 Significant evidence has been obtained that TRPV1 antagonists have anxiolytic activity in preclinical studies, but the antidepressant effect is not clear [6]. There is no direct evidence that TRP channels play a role in schizophrenia. However, the fact that TRPV1 channels play a role in central dopaminergic and cannabinoid mechanisms may suggests the potential role of these channels in schizophrenia [5]. CGRP release from trigeminal vasculature neuron network and neurogenic inflammatory response are currently accepted mechanisms for migraine attack pathophysiology. In particular, the TRP vanilloid 1 (TRPV1) and the TRP ankyrin 1 (TRPA1) are expressed in nociceptive neurons, which also express the sensory neuropeptides, tachykinins, and calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory responses. This evidence suggests that these channels may be an important therapeutic goal in migraine treatment [7].
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