α-synuclein accumulation in SH-SY5Y cell impairs autophagy in microglia by exosomes overloading miR-19a-3p
Tianen Zhou1, Danyu Lin2, Ying Chen3
1Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
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.
Insights
Exosomes from alpha-synuclein cells contain miR-19a-3p, which inhibits autophagy in microglia. This occurs by targeting the PTEN/AKT/mTOR pathway, suggesting a role in alpha-synucleinopathies.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Alpha-synucleinopathies are neurodegenerative diseases characterized by protein aggregation.
- Microglia play a crucial role in neuroinflammation and disease progression.
- Exosomes mediate intercellular communication and can transfer functional molecules like miRNAs.
Purpose of the Study:
- To investigate the role of exosomal miRNAs from alpha-synuclein transgenic cells in regulating microglial autophagy.
- To identify specific miRNAs involved in this process and their molecular targets.
Main Methods:
- Utilized microarray analysis to identify differentially expressed miRNAs in exosomes.
- Employed experimental verification to confirm the functional impact of identified miRNAs.
- Investigated the effect of exosomes and miR-19a-3p mimic on autophagy-related signaling pathways (PTEN/AKT/mTOR).
Main Results:
- miR-19a-3p was significantly upregulated in exosomes derived from alpha-synuclein transgenic SH-SY5Y cells.
- Exosomes and miR-19a-3p mimic inhibited phosphatase and tensin homolog (PTEN) expression.
- Increased phosphorylation of AKT and mTOR was observed, leading to autophagy dysfunction in recipient microglia.
Conclusions:
- Enhanced miR-19a-3p in exosomes suppresses autophagy in recipient microglia.
- This suppression is mediated by targeting the PTEN/AKT/mTOR signaling pathway.
- These findings highlight a novel mechanism of intercellular communication in alpha-synucleinopathies.
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