[Parkin deletion affects PINK1/Parkin-mediated mitochondrial autophagy to exacerbate neuroinflammation and accelerate progression of Parkinson's disease in mice].
[Parkin deletion affects PINK1/Parkin-mediated mitochondrial autophagy to exacerbate neuroinflammation and accelerate progression of Parkinson's disease in mice].
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Bengbu, CN · Author affiliation
Anhui Provincial Center for Neural Regeneration Technology and New Medical Materials Engineering Research, Bengbu Medical University, Bengbu 233000, China.Location evidence
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Original abstract
OBJECTIVES: To investigate the role of mitochondrial autophagy disorder caused by deletion of E3 ubiquitin ligase Parkin in neuroinflammation in a mouse model of MPTP-induced Parkinson's disease (PD). METHODS: Wild-type (WT) male C57BL/6 mice and Parkin-/- mice were given intraperitoneal injections with MPTP or PBS for 5 consecutive days, and the changes in motor behaviors of the mice were observed using open field test. The effects of Parkin deletion on PD development and neuroinflammation were evaluated using immunofluorescence and Western blotting. The changes of the PINK 1/Parkin signaling pathway in the midbrain substantia nigra of the mice were examined to explore the molecular mechanism of Parkin-mediated regulation of mitochondrial autophagy and its effect on neuroinflammation in PD mice. RESULTS: Compared with their WT counterparts, the Parkin-/- mice with MPTP injections exhibited significant impairment of motor function with decreased TH+ neurons, increased α-synuclein (α-syn) accumulation, and increased numbers of GFAP+ and I-ba1+ cells in the midbrain substantia nigra. Parkin deletion obviously affected PINK1/Parkin-mediated mitochondrial autophagy to result in significantly increased mtDNA and upregulated expressions of STING and NLRP3 inflammatosomes in the midbrain substantia nigra of MPTP-treated transgenic mice. CONCLUSIONS: Parkin deletion causes mitochondrial autophagy disorder to accelerate PD progression and exacerbates neuroinflammation in mice by affecting the PINK1/Parkin signaling pathway, suggesting the important role of Parkin in early pathogenesis of PD.