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外泌体及其在神经退行性疾病发生、发展和诊治中的作用

张鲁琳, 刘明欣, 谢俊霞, 宋宁^*

青岛大学基础医学院生理学与病理生理学系，脑科学与疾病研究院，青岛 266071

摘要

外泌体是一种直径在30~100 nm的细胞外膜性囊泡，由真核生物体内的多种细胞产生，其内含有蛋白质、脂质、核酸以及和起源细胞相关的物质等。外泌体能够携带起源细胞内成分并作用于邻近或远距离的细胞，从而实现生理及疾病状态下不同细胞间的信息交流。近年来，研究表明神经退行性疾病发病相关的错误折叠蛋白(如α-突触核蛋白、tau蛋白、β-淀粉样蛋白等)能够通过外泌体运输，从而促进这些蛋白在细胞间传播并传播至未病变区域，加快疾病进程。本综述着重阐述了外泌体的起源和组成、生物合成、分泌、功能，尤其是在神经退行性疾病发生和发展中的作用。除此之外，还探讨了外泌体作为生物标记物和药物传递载体在神经退行性疾病的诊断与治疗中的作用和前景。

关键词： 外泌体; 神经退行性疾病; 错误折叠蛋白; 生物标记物; 药物传递

分类号：R338;Q42;R741

Exosomes and their roles in neurodegenerative diseases: from pathogenic, diagnostic and therapeutical perspectives

ZHANG Lu-Lin, LIU Ming-Xin, XIE Jun-Xia, SONG Ning^*

Department of Physiology and Pathophysiology, Medical College; Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China

Abstract

Exosomes are extracellular membranous vesicles with a diameter of 30–100 nm derived from a variety of eukaryocytes. The cargo of exosomes includes proteins, lipids, nucleic acids, and substances of the cells from which they originate. They can transfer functional cargo to neighboring and distal cells, therefore contributing to intercellular communication in both physiological and pathological processes. In recent years, it was shown that exosomes in several neurodegenerative diseases are closely related to the transmission of disease-related misfolded proteins (such as α-synuclein, tau, amyloid β-protein, etc). These proteins are transported by exosomes, thus promoting the propagation to unaffected cells or areas and accelerating the progression of neurodegenerative diseases. This review focuses on the origin and composition, biological synthesis, secretion, function of exosomes, as well as their roles in the pathogenesis and progression of neurodegenerative diseases. In addition, we also discuss that exosomes can serve as biomarkers and drug delivery vehicles, and play a role in the diagnosis and treatment of neurodegenerative diseases. 

Key words: exosomes; neurodegenerative diseases; misfolded proteins; biomarkers; drug delivery

收稿日期：2018-08-22　　录用日期：2018-11-12

通讯作者：宋宁　　E-mail: ningsong@qdu.edu.cn

DOI: 10.13294/j.aps.2019.0008

引用本文：

张鲁琳, 刘明欣, 谢俊霞, 宋宁. 外泌体及其在神经退行性疾病发生、发展和诊治中的作用[J]. 生理学报 2019; 71 (3): 439-453.

ZHANG Lu-Lin, LIU Ming-Xin, XIE Jun-Xia, SONG Ning. Exosomes and their roles in neurodegenerative diseases: from pathogenic, diagnostic and therapeutical perspectives. Acta Physiol Sin 2019; 71 (3): 439-453 (in Chinese with English abstract).