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

Biochem Biophys Res Commun. 2019 Oct 1;517(4):642-647. doi: 10.1016/j.bbrc.2019.07.084. Epub 2019 Aug 8.

Abstract

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.

Keywords: MPP(+); Microglia-derived EVs; Mitochondrial fission/fusion; PD cell model; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Cell Line, Tumor
  • Cell Survival
  • Cell-Derived Microparticles / drug effects
  • Cell-Derived Microparticles / metabolism*
  • Cell-Derived Microparticles / ultrastructure
  • Dynamins / metabolism
  • Endocytosis
  • Humans
  • Immediate-Early Proteins / metabolism
  • Microglia / ultrastructure
  • Mitochondrial Dynamics / drug effects*
  • Neurons / pathology
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology*
  • Protein Aggregates*
  • Protein Serine-Threonine Kinases / metabolism
  • alpha-Synuclein / metabolism*

Substances

  • Immediate-Early Proteins
  • Protein Aggregates
  • alpha-Synuclein
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • DNM1L protein, human
  • Dynamins