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蜘蛛毒液肽介导的离子通道相关神经保护和镇痛作用。

Ion Channels-related Neuroprotection and Analgesia Mediated by Spider Venom Peptides.

机构信息

Center of Technology in Molecular Medicine, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

Department of Pharmacy, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, Brazil.

出版信息

Curr Protein Pept Sci. 2023;24(5):365-379. doi: 10.2174/1389203724666230328133102.

Abstract

Ion channels play critical roles in generating and propagating action potentials and in neurotransmitter release at a subset of excitatory and inhibitory synapses. Dysfunction of these channels has been linked to various health conditions, such as neurodegenerative diseases and chronic pain. Neurodegeneration is one of the underlying causes of a range of neurological pathologies, such as Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, brain injury, and retinal ischemia. Pain is a symptom that can serve as an index of the severity and activity of a disease condition, a prognostic indicator, and a criterion of treatment efficacy. Neurological disorders and pain are conditions that undeniably impact a patient's survival, health, and quality of life, with possible financial consequences. Venoms are the best-known natural source of ion channel modulators. Venom peptides are increasingly recognized as potential therapeutic tools due to their high selectivity and potency gained through millions of years of evolutionary selection pressure. Spiders have been evolving complex and diverse repertoires of peptides in their venoms with vast pharmacological activities for more than 300 million years. These include peptides that potently and selectively modulate a range of targets, such as enzymes, receptors, and ion channels. Thus, components of spider venoms hold considerable capacity as drug candidates for alleviating or reducing neurodegeneration and pain. This review aims to summarize what is known about spider toxins acting upon ion channels, providing neuroprotective and analgesic effects.

摘要

离子通道在产生和传播动作电位以及在兴奋性和抑制性突触的一部分中神经递质释放方面起着关键作用。这些通道的功能障碍与各种健康状况有关,如神经退行性疾病和慢性疼痛。神经退行性变是一系列神经病理学的潜在原因之一,如阿尔茨海默病 (AD)、帕金森病 (PD)、脑缺血、脑损伤和视网膜缺血。疼痛是一种症状,可以作为疾病严重程度和活动的指标、预后指标和治疗效果的标准。神经障碍和疼痛是不可否认会影响患者生存、健康和生活质量的情况,并可能带来经济后果。毒液是离子通道调节剂的最佳天然来源。由于毒液肽经过数百万年的进化选择压力获得了高选择性和效力,因此它们越来越被认为是潜在的治疗工具。蜘蛛在其毒液中进化出了复杂多样的肽库,具有 3 多亿年的广泛药理学活性。这些包括能够有效且选择性地调节一系列靶标(如酶、受体和离子通道)的肽。因此,蜘蛛毒液的成分具有作为减轻或缓解神经退行性变和疼痛的药物候选物的巨大潜力。本综述旨在总结已知的作用于离子通道的蜘蛛毒素,提供神经保护和镇痛作用。

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