Inhibition of MiR-421 Preserves Mitochondrial Function and Protects Against Parkinson's Disease Pathogenesis Via Pink1/Parkin-Dependent Mitophagy

Overview

Journal Dis Markers

Publisher Wiley

Specialty Biochemistry

Date 2022 Jun 6

PMID 35664430

Authors

Xiaolin Dong

Xianghua He

Li Yang

Qingyun Li

Yanming Xu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Mitochondria-Associated MicroRNAs and Parkinson's Disease.

Aaluri G, Choudhary Y, Kumar S Neurosci Insights. 2024; 19:26331055241254846.

PMID: 38800624 PMC: 11127579. DOI: 10.1177/26331055241254846.

Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.

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

Markers D Dis Markers. 2023; 2023:9865394.

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The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Parkinson's Disease.

Guedes B, Cardoso S, Esteves A Biomedicines. 2023; 11(5).

PMID: 37239020 PMC: 10215921. DOI: 10.3390/biomedicines11051349.

Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review).

Ma Z, Liang H, Hu B, Cai S, Yan D Int J Mol Med. 2023; 51(6).

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