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帕金森病基础研究的当前趋势:从线粒体、溶酶体到α-突触核蛋白。

Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein.

机构信息

Department of Neuroscience of Disease, Brain Research Institute, Niigata University, 1-757, Asahimachidori, Chuoku, Niigata, 951-8585, Japan.

Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto University, 54, Shogoin Kawahara-cho, Sakyoku, Kyoto, 606-8507, Japan.

出版信息

J Neural Transm (Vienna). 2024 Jun;131(6):663-674. doi: 10.1007/s00702-024-02774-2. Epub 2024 Apr 13.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and other brain regions. A key pathological feature of PD is the abnormal accumulation of α-synuclein protein within affected neurons, manifesting as Lewy bodies and Lewy neurites. Despite extensive research efforts spanning several decades, the underlying mechanisms of PD and disease-modifying therapies remain elusive. This review provides an overview of current trends in basic research on PD. Initially, it discusses the involvement of mitochondrial dysfunction in the pathogenesis of PD, followed by insights into the role of lysosomal dysfunction and disruptions in the vesicular transport system. Additionally, it delves into the pathological and physiological roles of α-synuclein, a crucial protein associated with PD pathophysiology. Overall, the purpose of this review is to comprehend the current state of elucidating the intricate mechanisms underlying PD and to outline future directions in understanding this disease.

摘要

帕金森病(PD)是一种神经退行性疾病,其特征是黑质和其他脑区的多巴胺能神经元进行性退化。PD 的一个关键病理特征是α-突触核蛋白在受影响神经元内的异常积累,表现为路易体和路易神经突。尽管几十年来进行了广泛的研究努力,但 PD 的潜在机制和疾病修饰疗法仍然难以捉摸。这篇综述提供了对 PD 基础研究当前趋势的概述。首先,它讨论了线粒体功能障碍在 PD 发病机制中的作用,然后深入探讨了溶酶体功能障碍和囊泡运输系统中断的作用。此外,它还探讨了α-突触核蛋白的病理和生理作用,α-突触核蛋白是与 PD 病理生理学相关的关键蛋白。总的来说,本综述的目的是了解阐明 PD 复杂机制的现状,并概述理解这种疾病的未来方向。

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