期刊
BIOMEDICINES
卷 8, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines8080272
关键词
amyloid propagation; amyloidogenesis; exosomes; extracellular vesicles; A beta peptide; C99; Alzheimer's disease; lysosomes; autophagy; endosomal sorting; proteostasis network; transmissible endosomal intoxication
资金
- NIH [AG057517]
- France Alzheimer [AAP-SM2018-1762]
In Alzheimer ' s disease (AD), endolysosomal dysfunctions are amongst the earliest cellular features to appear. Each organelle of the endolysosomal system, from the multivesicular body (MVB) to the lysosome, contributes to the homeostasis of amyloid precursor protein (APP) cleavage products including beta-amyloid (A beta) peptides. Hence, this review will attempt to disentangle how changes in the endolysosomal system cumulate to the generation of toxic amyloid species and hamper their degradation. We highlight that the formation of MVBs and the generation of amyloid species are closely linked and describe how the molecular machineries acting at MVBs determine the generation and sorting of APP cleavage products towards their degradation or release in association with exosomes. In particular, we will focus on AD-related distortions of the endolysomal system that divert it from its degradative function to favour the release of exosomes and associated amyloid species. We propose here that such an imbalance transposed at the brain scale poses a novel concept of transmissible endosomal intoxication (TEI). This TEI would initiate a self-perpetuating transmission of endosomal dysfunction between cells that would support the propagation of amyloid species in neurodegenerative diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据