Abstract
Aims: To reveal whether miRNAs in exosomes from α-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 α-synucleinopathies. Results: We found that miR-19a-3p increased remarkably in the exosomes from α-synuclein gene transgenic SH-SY5Y cells. Further study inferred that α-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.
Financial & competing interests disclosure
This work was supported by National Natural Science Foundation of China (grant numbers 81503052, 81571244, 81771378, 81971195), Basic and Applied Basic Research Project of Guangdong Province (grant number 2016A030313322), Natural Science Foundation of Guangdong Province (grant numbers 2017A030313840, 2017A030313459, 2018A0303130205), Fundamental Research Fund for University Youth Scholars (grant number 17ykpy39), Key Field Research and Development Program of Guangdong Province (grant numbers 2018B030337001), Yat-Sen Scholarship for Young Scientists, Key Laboratory of Malignant Tumor Molecular Mechanismand Translational Medicine of Guangzhou Bureau of Science and Information Technology (grant number [2013]163), and Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes (grant number KLB09001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Funded writing assistance was utilized in the production of this manuscript.