Department of Neurotherapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
J Biochem. 2021 Mar 5;169(2):181-186. doi: 10.1093/jb/mvaa131.
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and polyglutamine diseases are caused by aggregation and abnormal accumulation of the disease-causative proteins in brain and spinal cord. Recent studies have suggested that proteins associated with neurodegenerative diseases are secreted and transmitted intercellularly via extracellular vesicles (EVs), which may be involved in propagation of abnormal protein accumulation and progressive degeneration in patient brains. On the other hand, it has been also reported that EVs have neuroprotective roles in these diseases, which potentially contribute to preventing aggregation formation and aberrant accumulation of the disease-associated proteins. In this review, I summarize the current understanding of the roles of EVs in neurodegenerative diseases, especially focussing on the pathogenic and neuroprotective aspects. Elucidation of these two aspects of EVs would provide insight into not only potential therapeutic targets for treatment of neurodegenerative diseases but also development of EV-based biomarkers for disease diagnostics.
神经退行性疾病，如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和多聚谷氨酰胺疾病，是由大脑和脊髓中致病蛋白的聚集和异常积累引起的。最近的研究表明，与神经退行性疾病相关的蛋白质通过细胞外囊泡（EVs）被分泌和在细胞间传递，这可能与异常蛋白积累和患者大脑中进行性退化的传播有关。另一方面，也有报道称 EVs 在这些疾病中具有神经保护作用，这可能有助于防止与疾病相关的蛋白质的聚集形成和异常积累。在这篇综述中，我总结了 EVs 在神经退行性疾病中的作用的最新认识，特别是重点关注其致病和神经保护方面。阐明 EVs 的这两个方面不仅为神经退行性疾病的治疗提供了潜在的治疗靶点，也为基于 EV 的疾病诊断生物标志物的发展提供了思路。
