期刊
AGING AND DISEASE
卷 12, 期 6, 页码 1438-1450出版社
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2021.0516
关键词
alpha-synuclein; dopamine; dopaminergic neurons; exosomes; extracellular vesicles; EV engineering; EV targeting; motor deficits; neuroinflammation; Parkinson's disease; substantia nigra
资金
- National Institutes of Health [1R01NS106907]
- Department of Defense [W81XWH-17-1-0447, W81XWH-19-1-0548]
Extracellular vesicles shed by neurons and glia play crucial roles in neurodegenerative diseases, transferring pathological miRNAs and proteins while also serving as carriers for therapeutic drugs. They hold promise for both treatment and biomarker discovery in neurodegenerative diseases.
Extracellular vesicles (EVs) shed by neurons and glia in the central nervous system carry a cargo of specific bioactive molecules, facilitating intercellular communication. However, in neurodegenerative disease conditions, EVs carry pathological miRNAs and/or proteins involved in spreading the disease. Such EVs are also found in the cerebrospinal fluid (CSF) or the circulating blood, the characterization of which could identify biomarkers linked to specific neurodegenerative diseases. Moreover, EVs secreted by various stem/progenitor cells carry therapeutic miRNAs and proteins, which have shown promise to alleviate symptoms and slow down the progression of neurodegenerative diseases. The ability of exogenously administered EVs to easily cross the bloodbrain barrier with no risk for thrombosis and incorporate into neurons and glia has also opened up the possibility of using nano-sized EVs as carriers of therapeutic drugs or bioactive proteins. This review summarizes the role and function of EVs in alpha-synuclein-mediated neurodegeneration and the spread of alpha-synuclein from neurons to glia, leading to the activation of the inflammatory response in Parkinson's disease (PD). Moreover, the promise of brain-derived EVs in the CSF and the circulating blood for biomarker discovery and the efficacy of stem/progenitor cell-derived EVs or EVs loaded with bioactive molecules such as dopamine, catalase, curcumin, and siRNAs, in alleviating Parkinsonian symptoms are discussed.
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