自噬-溶酶体途径:帕金森病化学和基因治疗策略的潜在靶点

Fengjuan Jiao, Lingyan Meng, Kang Du, Xuezhi Li
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引用次数: 0

摘要

帕金森病是一种常见的神经退行性疾病,其运动障碍与神经元中α-突触核蛋白等聚集蛋白的胞浆内沉积有关。作为细胞内降解的主要途径之一,自噬-溶酶体途径在消除这些蛋白质方面发挥着重要作用。越来越多的证据表明,自噬-溶酶体途径的上调可能有助于清除α-突触核蛋白聚集体,并防止帕金森病中多巴胺能神经元的退化。此外,与帕金森病发病机制相关的多个基因与自噬-溶酶体途径的改变密切相关。因此,该通路似乎是治疗帕金森病的一个很有前景的治疗靶点。在本综述中,我们将简要介绍自噬机制。然后,我们描述了帕金森病相关基因对自噬-溶酶体途径的影响。最后,我们强调了针对自噬-溶酶体途径的潜在化学和基因治疗策略及其在帕金森病中的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The autophagy-lysosome pathway: a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease. Moreover, multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson’s disease-related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy-lysosome pathway and their applications in Parkinson’s disease.
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