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SCIENTIFIC LITERATURE · MED

Adult Conditional Knockout of PGC-1α Leads to Loss of Dopamine Neurons.

eNeuro · 2016-07-01

DOI: 10.1523/eneuro.0183-16.2016PMID: 27622213

Open accessResearch Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., ExtramuralOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated a role for peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α) in PD and in animal or cellular models of PD. The role of PGC-1α in the function and survival of substantia nigra pars compacta (SNpc) dopamine neurons is not clear. Here we find that there are four different PGC-1α isoforms expressed in SH-SY5Y cells, and these four isoforms are expressed across subregions of mouse brain. Adult conditional PGC-1α knock-out mice show a significant loss of dopaminergic neurons that is accompanied by a reduction of dopamine in the striatum. In human PD postmortem tissue from the SNpc, there is a reduction of PGC-1α isoforms and mitochondria markers. Our findings suggest that all four isoforms of PGC-1α are required for the proper expression of mitochondrial proteins in SNpc DA neurons and that PGC-1α is essential for SNpc DA neuronal survival, possibly through the maintenance of mitochondrial function.

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