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内源性分泌的巨囊泡减少 Aβ 负担并改善阿尔茨海默病。

Secreted endogenous macrosomes reduce Aβ burden and ameliorate Alzheimer's disease.

机构信息

School of Biomedical Engineering, Liaoning Key Lab of Integrated Circuit and Biomedical Electronic System, Dalian University of Technology, Lingshui Road, Dalian 116024, P. R. China.

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China.

出版信息

Sci Adv. 2023 May 26;9(21):eade0293. doi: 10.1126/sciadv.ade0293.

DOI:10.1126/sciadv.ade0293
PMID:37235655
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10219594/
Abstract

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.

摘要

由于人口老龄化规模不断扩大以及缺乏有效的药物治疗，目前迫切需要针对阿尔茨海默病（AD）的创新治疗策略。在这里，我们报告了由小胶质细胞分泌的细胞外囊泡（EVs），包括巨囊泡和小 EVs，对 AD 相关病理的治疗效果。巨囊泡强烈抑制β-淀粉样蛋白（Aβ）聚集，并挽救细胞免受 Aβ错误折叠诱导的细胞毒性。此外，巨囊泡给药减少了 Aβ斑块并改善了 AD 小鼠的认知障碍。相比之下，小 EVs 略微促进 Aβ聚集，并且不能改善 AD 病理。小 EVs 和巨囊泡的蛋白质组分析表明，巨囊泡中含有几种抑制 Aβ错误折叠的重要神经保护蛋白。特别是，巨囊泡中的小整合膜蛋白 10 样蛋白 2B 已被证明可以抑制 Aβ聚集。我们的观察结果为治疗 AD 提供了一种替代传统无效药物治疗的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/7edaacc0ab39/sciadv.ade0293-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/7eb58b0dcdd4/sciadv.ade0293-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/b14d19769870/sciadv.ade0293-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/15618e8ab2fa/sciadv.ade0293-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/628ede05442e/sciadv.ade0293-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/aef248cbd317/sciadv.ade0293-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/5e1026a1aba2/sciadv.ade0293-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/7edaacc0ab39/sciadv.ade0293-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/7eb58b0dcdd4/sciadv.ade0293-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/b14d19769870/sciadv.ade0293-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/15618e8ab2fa/sciadv.ade0293-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/628ede05442e/sciadv.ade0293-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/aef248cbd317/sciadv.ade0293-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/5e1026a1aba2/sciadv.ade0293-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac82/10219594/7edaacc0ab39/sciadv.ade0293-f7.jpg

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引用本文的文献

[1]
Extracellular Vesicles for the Treatment of Alzheimer's Disease: A Systematic Review.

J Extracell Biol. 2025-8-20

[2]
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J Cent Nerv Syst Dis. 2025-4-23

[3]
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Front Med (Lausanne). 2025-1-29

[4]
Application of Multiomics Approach to Investigate the Therapeutic Potentials of Stem Cell-derived Extracellular Vesicle Subpopulations for Alzheimer's Disease.

bioRxiv. 2024-5-14

[5]
Hybrid Membrane-Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease.

Adv Sci (Weinh). 2024-6

[6]
Cooperative effects of SIRT1 and SIRT2 on APP acetylation.

Aging Cell. 2023-10

[7]
A highly sensitive nanochannel device for the detection of SUMO1 peptides.

Chem Sci. 2023-7-13

本文引用的文献

[1]
Human Microglia Extracellular Vesicles Derived from Different Microglia Cell Lines: Similarities and Differences.

ACS Omega. 2022-6-28

[2]
Exosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake.

J Control Release. 2022-7

[3]
Boosting extracellular vesicle secretion.

Biotechnol Adv. 2022-10

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Illuminating Neural Circuits in Alzheimer's Disease.

Neurosci Bull. 2021-8

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Brain Targeting and Aβ Binding Bifunctional Nanoparticles Inhibit Amyloid Protein Aggregation in APP/PS1 Transgenic Mice.

ACS Chem Neurosci. 2021-6-16

[6]
Microglia use TAM receptors to detect and engulf amyloid β plaques.

Nat Immunol. 2021-5

[7]
Peptidomimetic-Based Vesicles Inhibit Amyloid-β Fibrillation and Attenuate Cytotoxicity.

J Am Chem Soc. 2021-3-3

[8]
-GlcNAcylation ameliorates the pathological manifestations of Alzheimer's disease by inhibiting necroptosis.

Sci Adv. 2021-1-13

[9]
Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA.

Biomater Sci. 2021-6-15

[10]
Chiral gold nanoparticles enantioselectively rescue memory deficits in a mouse model of Alzheimer's disease.

Nat Commun. 2020-9-22

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