帕金森病中α-突触核蛋白与膜的相互作用：机制与治疗策略。

IF 5.1 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2024-08-22 DOI:10.1016/j.nbd.2024.106646

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引用次数: 0

摘要

帕金森病（PD）是全球第二大最常见的神经退行性疾病，其特征是路易体和路易神经节的存在，神经元病变含有大量突触蛋白α-突触核蛋白（αS）。虽然帕金森氏症疾病进展的基本机制仍不清楚，但越来越多的证据支持αS与细胞膜之间的相互作用在帕金森氏症病理学中的重要性。因此，了解αS与细胞膜在健康和疾病中的相互作用对于制定治疗策略至关重要。在这篇综述中，我们（1）讨论了病理αS-膜相互作用的关键情景；（2）详细介绍了明确报道的改变αS-膜相互作用的治疗策略；（3）介绍了可能涉及干扰αS-膜相互作用的其他治疗策略。通过这种方式，我们旨在从整体角度探讨针对帕金森病和其他α-突触核蛋白病的疾病修饰策略的这一重要方面。

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Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies

Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, is marked by the presence of Lewy bodies and Lewy neurites, neuronal lesions containing large amounts of the synaptic protein alpha-synuclein (αS). While the underlying mechanisms of disease progression in PD remain unclear, increasing evidence supports the importance of interactions between αS and cellular membranes in PD pathology. Therefore, understanding the αS-membrane interplay in health and disease is crucial for the development of therapeutic strategies. In this review, we (1) discuss key scenarios of pathological αS-membrane interactions; (2) present in detail therapeutic strategies explicitly reported to modify αS-membrane interactions; and (3) introduce additional therapeutic strategies that may involve aspects of interfering with αS-membrane interaction. This way, we aim to provide a holistic perspective on this important aspect of disease-modifying strategies for PD and other α-synucleinopathies.

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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.