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• W4308624832 abstract "SLC1A5 variant (SLC1A5_var) is identified as a mitochondrial glutamine transporter in cancer cells recently. However, the role of SLC1A5_var in Parkinson's disease (PD) is completely unknown. Here, we found the significant downregulation of SLC1A5_var in astrocytes and midbrain of mice treated with MPTP/MPP+ and LPS. Importantly, overexpression of SLC1A5_var ameliorated but knockdown of SLC1A5_var exacerbated MPTP/MPP+- and LPS-induced mitochondrial dysfunction. Consequently, SLC1A5_var provided beneficial effects on PD pathology including improvement of PD-like motor symptoms and rescue of dopaminergic (DA) neuron degeneration through maintaining mitochondrial energy metabolism. Moreover, SLC1A5_var reduced astrocyte reactivity via inhibition of A1 astrocyte conversion. Further investigation demonstrated that SLC1A5_var restrained the secretion of astrocytic pro-inflammatory cytokines by blunting TLR4-mediated downstream pathways. This is the first study to prove that astrocytic SLC1A5_var inhibits neuroinflammation, and rescues the loss of DA neurons and motor symptoms involved in PD progression, which provides a novel target for PD treatment." @default.
• W4308624832 created "2022-11-13" @default.
• W4308624832 creator A5001990780 @default.
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• W4308624832 date "2022-11-09" @default.
• W4308624832 modified "2023-10-16" @default.
• W4308624832 title "Mitochondrial glutamine transporter SLC1A5_var, a potential target to suppress astrocyte reactivity in Parkinson’s Disease" @default.
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• W4308624832 doi "https://doi.org/10.1038/s41419-022-05399-z" @default.
• W4308624832 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36351889" @default.
• W4308624832 hasPublicationYear "2022" @default.
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