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 alpha-synuclein (alpha-Syn) leads to enhanced neurotoxicity. However, the function of EVs derived from microglia not treated with aggregated alpha-Syn or treated with monomeric alpha-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 alpha-Syn, appeared to be protective, and the mechanisms, though remain to be defined further, appeared to involve mitochondrial dynamics, especially mitochondrial fission. (C) 2019 Elsevier Inc. All rights reserved.