Inhibition of miR-421 Preserves Mitochondrial Function and Protects against Parkinson’s Disease Pathogenesis via Pink1/Parkin-Dependent Mitophagy

Autor:	Xiaolin Dong, Xianghua He, Li Yang, Qingyun Li, Yanming Xu
Rok vydání:	2022
Předmět:	Article Subject Ubiquitin-Protein Ligases Biochemistry (medical) Clinical Biochemistry Mitophagy Parkinson Disease General Medicine Mitochondria nervous system diseases Mice MicroRNAs Neuroblastoma 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Genetics Animals Humans Protein Kinases Molecular Biology
Zdroj:	Disease Markers. 2022:1-13
ISSN:	1875-8630 0278-0240
DOI:	10.1155/2022/5186252
Popis:	Mutations in PINK1 and Parkin are a major cause of Parkinson’s disease (PD) pathogenesis. In addition, PINK1 and Parkin are two mitochondrial proteins that jointly contribute to mitochondrial homeostasis via mitophagy. Mitochondrial dysfunction is the most significant mechanism underlying PD pathogenesis. Thus, understanding the regulatory mechanism of PINK1 and Parkin expression is beneficial to the treatment of PD. In this study, we found that miR-421 expression was upregulated in mice treated with MPTP, as well as in SH-SY5Y cells treated with methyl-4-phenylpyridine (MPP+). Inhibition of miR-421 alleviated neurodegeneration in MPTP-treated mice and promoted mitophagy in MPP+-treated SH-SY5Y cells. Bioinformatics software predicted that Pink1 is a downstream target protein of miR-421. In addition, miR-421-induced Pink1 and Parkin inhibition negatively modulates mitophagy in MPP+-treated SH-SY5Y cells. In addition, our study confirmed that Pink1/Parkin is responsible for miR-421-regulated cell mitophagy. Overall, this study revealed that miR-421 regulates nerve cell mitophagy through the Pink1/Parkin pathway.
Databáze:	OpenAIRE
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