Vella Laura J, Sharples Robyn A, Nisbet Rebecca M, Cappai Roberto, Hill Andrew F
Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
Eur Biophys J. 2008 Mar;37(3):323-32. doi: 10.1007/s00249-007-0246-z. Epub 2007 Dec 7.
Exosomes are small membranous vesicles secreted by a number of cell types and can be isolated from conditioned cell media or bodily fluids such as urine and plasma. Exosome biogenesis involves the inward budding of multivesicular bodies (MVB) to form intraluminal vesicles (ILV). When fused with the plasma membrane, the MVB releases the vesicles into the extracellular environment as exosomes. Proposed functions of these vesicles include roles in cell-cell signalling, removal of unwanted proteins, and the transfer of pathogens between cells, such as HIV-1. Another such pathogen which exploits this pathway is the prion, the infectious particle responsible for the transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform encephalopathy (BSE) of cattle. Interestingly, this work is mirrored by studies on another protein involved in neurodegenerative disease, the amyloid precursor protein (APP) which is associated with Alzheimer's disease (AD). Recent work has found APP proteolytic fragments in association with exosomes, suggesting a common pathway previously unknown for proteins associated with neurodegenerative diseases. This review will be discussing the current literature regarding the role of exosomes in secretion of the proteins, PrP and APP, and the subsequent implications for neurodegenerative disease.
外泌体是由多种细胞类型分泌的小膜泡，可从条件培养基或尿液和血浆等体液中分离出来。外泌体生物发生涉及多泡体（MVB）向内出芽形成腔内小泡（ILV）。当与质膜融合时，MVB将小泡作为外泌体释放到细胞外环境中。这些小泡的功能包括细胞间信号传导、清除不需要的蛋白质以及细胞间病原体的转移，如HIV-1。另一种利用这一途径的病原体是朊病毒，它是导致人类克雅氏病（CJD）或牛海绵状脑病（BSE）等可传播神经退行性疾病的感染性颗粒。有趣的是，关于另一种与神经退行性疾病有关的蛋白质——淀粉样前体蛋白（APP）的研究也反映了这一工作，APP与阿尔茨海默病（AD）有关。最近的研究发现APP蛋白水解片段与外泌体有关，这表明与神经退行性疾病相关的蛋白质以前未知的共同途径。本综述将讨论有关外泌体在蛋白质PrP和APP分泌中的作用以及对神经退行性疾病的后续影响的当前文献。
