Extracellular microvesicles-derived from microglia treated with unaggregated α-synuclein attenuate mitochondrial fission and toxicity-induced by Parkinsonian toxin MPP

• Published in: Biochemical and biophysical research communications Vol. 517; no. 4; pp. 642 - 647
• Main Authors: Li, Na, Wu, Yufeng, Zhu, Liangyi, Huang, Yang, Liu, Zongran, Shi, Min, Soltys, David, Zhang, Jing, Chang, Qing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Microglia-derived EVs; mitochondria; Mitochondrial fission/fusion; MPP; neuroglia; neurotoxicity; Parkinson disease; PD cell model; toxins; α-synuclein; EV(+); EV(−); Microglia-derived EVs; PD cell model; MPP; α-synuclein; Mitochondrial fission/fusion; MPP(+)
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2019.07.084

Biological functions of extracellular vesicles (EVs) are being discovered to be critical in neurodegenerative disorders, including Parkinson's disease (PD). A previous study using cellular models of PD has suggested that EVs derived from microglia exposed to aggregated α-synuclein (α-Syn) leads to enhanced neurotoxicity. However, the function of EVs derived from microglia not treated with aggregated a-Syn or treated with monomeric α-Syn are unclear. Here, employing a widely used cellular model of PD, i.e. SH-SY5Y cells treated with MPP+, a well-established parkinsonian toxicant, we revealed that microglial EVs, when not stimulated by aggregated α-Syn, appeared to be protective, and the mechanisms, though remain to be defined further, appeared to involve mitochondrial dynamics, especially mitochondrial fission. •MPP+, a parkinsonian toxicant, may induce neuronal cell injury via regulating the SGK1-FOXO3a pathway, promoting generation of reactive oxygen species and inflicting mitochondrial dynamics imbalance, with enhanced mitochondrial fission.•Microglial EVs, isolated from media after treatment with unaggregated α-synuclein, could be internalized by cultured neurons.•EVs isolated from microglia treated with unaggregated α-synuclein attenuated the neurotoxicity.