Objective: The aim of this study was to investigate whether the exosomes secreted by dopaminergic neurons over-expressing α-synuclein could regulate the inflammation of microglia via autophagy.
Background: As important meditators of intercellular communication, exosomes play a crucial role in the development and progression of Parkinson’s disease (PD). The cargo of exosomes is comprised of various functionally active molecules, such as misfolded protein, lncRNA, and mRNA, can alter biological signaling pathways in recipient cells.
Method: SHSY5Y cells were transfected with either lentivirus expressing wild-type human SNCA or control lentivirus. Their derived exosomes were isolated by ultracentrifugation and then incubated with human microglia (HM), respectively. Western blots (WB) were used to detect the expression of autophagy related proteins and MAPK signal pathways in microglia. After LC3 immunofluorescence staining, the fluorescence signal was observed by confocal laser. The levels of IL-1 β and IL-6 released by microglia were detected by ELISA.
Results: Here, we showed that the exosomes from α-synuclein gene transgenic SH-SY5Y cells (SNCA-Tg) significantly enhanced the expression of p62 and decreased LC3-II / I ratio in microglia when compared to control group. Furthermore, the results of fluorescence microscope revealed that red fluorescence of LC3 was significantly decreased in HM cells exposed to SNCA-Tg exosomes. Moreover, the secretion of inflammatory factors and phosphorylation of JNK obviously increased in HM cells 48 hours after exposed to exosomes devised from SHSY5Y cells overexpressing α-synuclein, however, this effect was reversed when HM cells were co-incubation with autophagy inducer rapamycin.
Conclusion: In conclusion, the results of the present study suggest that exosomes from neurons overexpressing α-synuclein may modulate microglial inflammation via autophagy. Exosomes in central nervious system may serve as therapeutic targets for neurodegenerative diseases including PD.
To cite this abstract in AMA style:
Y. Liang, L. Bu, E. Tao. Effects of exosomes devised from dopaminergic neurons overexpressing α-synuclein on autophagy and inflammation in microglia [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/effects-of-exosomes-devised-from-dopaminergic-neurons-overexpressing-%ce%b1-synuclein-on-autophagy-and-inflammation-in-microglia/. Accessed May 24, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-exosomes-devised-from-dopaminergic-neurons-overexpressing-%ce%b1-synuclein-on-autophagy-and-inflammation-in-microglia/