Wycombe Abbey, Buckinghamshire HP11 1PE, UK.
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Neurobiol Dis. 2024 Oct 15;201:106646. doi: 10.1016/j.nbd.2024.106646. Epub 2024 Aug 22.
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.
帕金森病（PD）是全球第二常见的神经退行性疾病，其特征是存在路易体和路易神经纤维，神经元损伤含有大量突触蛋白α-突触核蛋白（αS）。虽然 PD 疾病进展的潜在机制尚不清楚，但越来越多的证据支持αS 与细胞膜之间相互作用在 PD 病理学中的重要性。因此，了解健康和疾病中αS-膜相互作用对于治疗策略的发展至关重要。在这篇综述中，我们 (1) 讨论了病理性αS-膜相互作用的关键情况；(2) 详细介绍了明确报道的可修饰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。这样，我们旨在为 PD 和其他α-突触核蛋白病的疾病修饰策略的这一重要方面提供一个整体视角。
