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神经毒素与神经毒性机制。综述

Neurotoxins and neurotoxicity mechanisms. An overview.

作者信息

Segura-Aguilar Juan, Kostrzewa Richard M

机构信息

Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Casilla 70000, Santiago, Chile.

出版信息

Neurotox Res. 2006 Dec;10(3-4):263-87. doi: 10.1007/BF03033362.

Abstract

Neurotoxins represent unique chemical tools, providing a means to 1) gain insight into cellular mechanisms of apopotosis and necrosis, 2) achieve a morphological template for studies otherwise unattainable, 3) specifically produce a singular phenotype of denervation, and 4) provide the starting point to delve into processes and mechanisms of nerve regeneration and sprouting. There are many other notable uses of neurotoxins in neuroscience research, and ever more being discovered each year. The objective of this review paper is to highlight the broad areas of neuroscience in which neurotoxins and neurotoxicity mechanism come into play. This shifts the focus away from neurotoxins per se, and onto the major problems under study today. Neurotoxins broadly defined are used to explore neurodegenerative disorders, psychiatric disorders and substance use disorders. Neurotoxic mechanisms relating to protein aggregates are indigenous to Alzheimer disease, Parkinson's disease. NeuroAIDS is a disorder in which microglia and macrophages have enormous import. The gap between the immune system and nervous system has been bridged, as neuroinflammation is now considered to be part of the neurodegenerative process. Related mechanisms now arise in the process of neurogenesis. Accordingly, the entire spectrum of neuroscience is within the purview of neurotoxins and neurotoxicity mechanisms. Highlights on discoveries in the areas noted, and on selective neurotoxins, are included, mainly from the past 2 to 3 years.

摘要

神经毒素是独特的化学工具,可用于以下几个方面:1)深入了解细胞凋亡和坏死的机制;2)获得其他方法难以实现的形态学研究模板;3)特异性产生单一的去神经表型;4)为深入研究神经再生和发芽的过程及机制提供起点。神经毒素在神经科学研究中还有许多其他显著用途,并且每年都有更多新用途被发现。本文综述的目的是突出神经毒素及其神经毒性机制在神经科学中发挥作用的广泛领域。这将关注点从神经毒素本身转移到了当今正在研究的主要问题上。广义上定义的神经毒素被用于探索神经退行性疾病、精神疾病和物质使用障碍。与蛋白质聚集体相关的神经毒性机制在阿尔茨海默病、帕金森病中很常见。神经艾滋病是一种小胶质细胞和巨噬细胞具有重要作用的疾病。免疫系统和神经系统之间的差距已经被弥合,因为神经炎症现在被认为是神经退行性过程的一部分。相关机制现在也出现在神经发生过程中。因此,神经科学的整个领域都在神经毒素和神经毒性机制的研究范围内。本文主要介绍了过去两到三年在上述领域以及一些选择性神经毒素方面的发现亮点。

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