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• W1986579963 abstract "Parkinson9s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Mitochondrial complex I impairment in PD is modeled <i>in vitro</i> by the susceptibility of dopaminergic neurons to the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+). In the present study, we demonstrate that microRNA-7 (miR-7), which is expressed in tyrosine hydroxylase-positive nigral neurons in mice and humans, protects cells from MPP+-induced toxicity in dopaminergic SH-SY5Y cells, differentiated human neural progenitor ReNcell VM cells, and primary mouse neurons. RelA, a component of nuclear factor-κB (NF-κB), was identified to be downregulated by miR-7 using quantitative proteomic analysis. Through a series of validation experiments, it was confirmed that RelA mRNA is a target of miR-7 and is required for cell death following MPP+ exposure. Further, RelA mediates MPP+-induced suppression of NF-κB activity, which is essential for MPP+-induced cell death. Accordingly, the protective effect of miR-7 is exerted through relieving NF-κB suppression by reducing RelA expression. These findings provide a novel mechanism by which NF-κB suppression, rather than activation, underlies the cell death mechanism following MPP+ toxicity, have implications for the pathogenesis of PD, and suggest miR-7 as a therapeutic target for this disease." @default.
• W1986579963 created "2016-06-24" @default.
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• W1986579963 date "2014-09-17" @default.
• W1986579963 modified "2023-09-26" @default.
• W1986579963 title "MicroRNA-7 Protects against 1-Methyl-4-Phenylpyridinium-Induced Cell Death by Targeting RelA" @default.
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• W1986579963 doi "https://doi.org/10.1523/jneurosci.0985-14.2014" @default.
• W1986579963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4166159" @default.
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