Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Gerontology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Pharmacol Res. 2021 Mar;165:105469. doi: 10.1016/j.phrs.2021.105469. Epub 2021 Jan 30.
The communication between neurons constitutes the basis of all neural activities, and synaptic vesicle exocytosis is the fundamental biological event that mediates most communication between neurons in the central nervous system. The SNARE complex is the core component of the protein machinery that facilitates the fusion of synaptic vesicles with presynaptic terminals and thereby the release of neurotransmitters. In synapses, each release event is dependent on the assembly of the SNARE complex. In recent years, basic research on the SNARE complex has provided a clearer understanding of the mechanism underlying the formation of the SNARE complex and its role in vesicle formation. Emerging evidence indicates that abnormal expression or dysfunction of the SNARE complex in synapse physiology might contribute to abnormal neurotransmission and ultimately to synaptic dysfunction. Clinical research using postmortem tissues suggests that SNARE complex dysfunction is correlated with various neurological diseases, and some basic research has also confirmed the important role of the SNARE complex in the pathology of these diseases. Genetic and pharmacogenetic studies suggest that the SNARE complex and individual proteins might represent important molecular targets in neurological disease. In this review, we summarize the recent progress toward understanding the SNARE complex in regulating membrane fusion events and provide an update of the recent discoveries from clinical and basic research on the SNARE complex in neurodegenerative, neuropsychiatric, and neurodevelopmental diseases.
神经元之间的通讯构成了所有神经活动的基础，而突触小泡胞吐是介导中枢神经系统中大多数神经元之间通讯的基本生物学事件。SNARE 复合体是促进突触小泡与突触前末端融合从而释放神经递质的蛋白质机器的核心组成部分。在突触中，每个释放事件都依赖于 SNARE 复合体的组装。近年来，对 SNARE 复合体的基础研究提供了对 SNARE 复合体形成机制及其在囊泡形成中的作用的更清晰理解。新出现的证据表明，突触生理学中 SNARE 复合体的异常表达或功能障碍可能导致异常的神经传递，并最终导致突触功能障碍。使用尸检组织的临床研究表明，SNARE 复合体功能障碍与各种神经疾病相关，一些基础研究也证实了 SNARE 复合体在这些疾病病理中的重要作用。遗传和药理学研究表明，SNARE 复合体和单个蛋白质可能代表神经疾病的重要分子靶点。在这篇综述中，我们总结了近年来对 SNARE 复合体在调节膜融合事件中的作用的理解进展，并提供了对神经退行性、神经精神和神经发育性疾病中 SNARE 复合体的临床和基础研究的最新发现的更新。
