Chaudhuri et al. (2014). Journal of Neuroscience. doi: 10.1523/jneurosci.0985-14.2014
…RelA J. Neurosci., September 17, 2014 • 34(38):12725–12737 • 12727 Related Disorders at the Banner Sun Health Research Institute. Incuba- tion with rabbit anti-TH antibody (1:500; catalog #P40101-0, Pel-Freez Biologicals) for IF labeling was performed along with anti-digoxigenin- POD antibody. Tissue sections were incubated with anti-rabbit-TRITC secondary antibody (1:1000; catalog #T6778, Sigma) for IF labeling…
Pel-Freez products cited: Rabbit Anti-Tyrosine Hydroxylase (P40101)
Abstract
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Mitochondrial complex I impairment in PD is modeled in vitro 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.