Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Zhejiang, China.
Trends Neurosci. 2024 Sep;47(9):693-707. doi: 10.1016/j.tins.2024.06.005. Epub 2024 Jul 23.
Synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), are characterized by neuronal loss accompanied by α-synuclein (α-syn) accumulation in the brain. While research conventionally focused on brain pathology, there is growing interest in peripheral alterations. Erythrocytes, which are rich in α-syn, have emerged as a compelling site for synucleinopathies-related alterations. Erythrocyte-derived extracellular vesicles (EVs), containing pathological α-syn species, can traverse the blood-brain barrier (BBB) under certain conditions and the gastrointestinal tract, where α-syn and gut microbiota interact extensively. This review explores the accumulating evidence of erythrocyte involvement in synucleinopathies, as well as their potential in disease pathogenesis and diagnosis. Given their unique properties, erythrocytes and erythrocyte-derived EVs may also serve as an ideal therapeutic platform for treating synucleinopathies and beyond.
突触核蛋白病包括帕金森病(PD)、多系统萎缩(MSA)和路易体痴呆(DLB),其特征是神经元丧失,伴有脑内α-突触核蛋白(α-syn)的积累。虽然研究传统上集中于脑部病理学,但人们对周围改变的兴趣日益增加。富含α-syn 的红细胞已成为突触核蛋白病相关改变的一个引人注目的部位。红细胞衍生的细胞外囊泡(EVs)含有病理性α-syn 物种,在某些条件下可以穿透血脑屏障(BBB)和胃肠道,在那里α-syn 与肠道微生物群广泛相互作用。本综述探讨了红细胞参与突触核蛋白病的累积证据,以及它们在疾病发病机制和诊断中的潜在作用。鉴于其独特的性质,红细胞和红细胞衍生的 EVs 也可能成为治疗突触核蛋白病及其他疾病的理想治疗平台。