α-synuclein accumulation in SH-SY5Y cell impairs autophagy in microglia by exosomes overloading miR-19a-3p

Aims: To reveal whether miRNAs in exosomes from alpha-synuclein transgenic SH-SY5Y cells are able to regulate autophagy in recipient microglia. Materials & methods: Microarray analysis and experimental verification were adopted to assess the significance of autophagy-associated miRNAs in exosomes from neuronal model of alpha-synucleinopathies. Results: We found that miR-19a-3p increased remarkably in the exosomes from alpha-synuclein gene transgenic SH-SY5Y cells. Further study inferred that alpha-synuclein gene transgenic SH-SY5Y cell-derived exosomes and miR-19a-3p mimic consistently inhibited the expression of phosphatase and tensin homolog and increased the phosphorylation of AKT and mTOR, both of which ultimately lead to the dysfunction of autophagy in recipient microglia. Conclusion: The data suggested that enhanced expression of miR-19a-3p in exosomes suppress autophagy in recipient microglia by targeting the phosphatase and tensin homolog/AKT/mTOR signaling pathway.