Статья

Secreted endogenous macrosomes reduce Aβ burden and ameliorate Alzheimer’s disease

Cunli WangKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. ChinaYiming YangSchool of Biomedical Engineering, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Lingshui Road, Dalian 116024, P. R. ChinaXiaoyu ZhangKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. ChinaZhenqiang ShiKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. ChinaHuiling GaoCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. ChinaManli ZhongCollege of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. ChinaYonggang FanHealth Sciences Institute, Key Laboratory of Major Chronic Diseases of Nervous System, China Medical University, Shenyang, 110122, P. R. ChinaHongyan ZhangKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. ChinaBo LiuSchool of Biomedical Engineering, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Lingshui Road, Dalian 116024, P. R. ChinaGuangyan QingKey Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, P. R. China

2023en

ABI

Аннотация

Innovative therapeutic strategies are urgently needed for Alzheimer's disease (AD) due to the increasing size of the aging population and the lack of effective drug treatment. Here, we report the therapeutic effects of extracellular vesicles (EVs) secreted by microglia, including macrosomes and small EVs, on AD-associated pathology. Macrosomes strongly inhibited β-amyloid (Aβ) aggregation and rescued cells from Aβ misfolding-induced cytotoxicity. Furthermore, macrosome administration reduced Aβ plaques and ameliorated cognitive impairment in mice with AD. In contrast, small EVs slightly promoted Aβ aggregation and did not improve AD pathology. Proteomic analysis of small EVs and macrosomes revealed that macrosomes harbor several important neuroprotective proteins that inhibit Aβ misfolding. In particular, the small integral membrane protein 10-like protein 2B in macrosomes has been shown to inhibit Aβ aggregation. Our observations provide an alternative therapeutic strategy for the treatment of AD over conventional ineffective drug treatments.

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Идентификаторы

DOI: 10.1126/sciadv.ade0293

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar