Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Laboratory of Applied Proteome Analyses and Research Center PIGMOD, Rumburska 89, 277 21 Libechov, Czech Republic.
Int J Mol Sci. 2021 Apr 15;22(8):4085. doi: 10.3390/ijms22084085.
Huntington's disease (HD) is a rare hereditary autosomal dominant neurodegenerative disorder, which is caused by expression of mutant huntingtin protein (mHTT) with an abnormal number of glutamine repeats in its N terminus, and characterized by intracellular mHTT aggregates (inclusions) in the brain. Exosomes are small extracellular vesicles that are secreted generally by all cell types and can be isolated from almost all body fluids such as blood, urine, saliva, and cerebrospinal fluid. Exosomes may participate in the spreading of toxic misfolded proteins across the central nervous system in neurodegenerative diseases. In HD, such propagation of mHTT was observed both in vitro and in vivo. On the other hand, exosomes might carry molecules with neuroprotective effects. In addition, due to their capability to cross blood-brain barrier, exosomes hold great potential as sources of biomarkers available from periphery or carriers of therapeutics into the central nervous system. In this review, we discuss the emerging roles of exosomes in HD pathogenesis, diagnosis, and therapy.
亨廷顿病（HD）是一种罕见的遗传性常染色体显性神经退行性疾病，由其 N 端异常数量的谷氨酰胺重复的突变亨廷顿蛋白（mHTT）表达引起，并以脑内的细胞内 mHTT 聚集体（包涵体）为特征。外泌体是由所有细胞类型普遍分泌的小细胞外囊泡，可从血液、尿液、唾液和脑脊液等几乎所有体液中分离出来。外泌体可能参与了神经退行性疾病中有毒错误折叠蛋白在中枢神经系统中的传播。在 HD 中，已经在体外和体内观察到 mHTT 的这种传播。另一方面，外泌体可能携带具有神经保护作用的分子。此外，由于其穿过血脑屏障的能力，外泌体作为可从外周获得的生物标志物的来源或作为中枢神经系统治疗药物的载体具有巨大的潜力。在这篇综述中，我们讨论了外泌体在 HD 发病机制、诊断和治疗中的新作用。
