RT Journal Article
SR Electronic
T1 Adult Conditional Knockout of PGC-1α Leads to Loss of Dopamine Neurons
JF eneuro
JO eneuro
FD Society for Neuroscience
SP ENEURO.0183-16.2016
DO 10.1523/ENEURO.0183-16.2016
VO 3
IS 4
A1 Haisong Jiang
A1 Sung-Ung Kang
A1 Shuran Zhang
A1 Senthilkumar Karuppagounder
A1 Jinchong Xu
A1 Yong-Kyu Lee
A1 Bong-Gu Kang
A1 Yunjong Lee
A1 Jianmin Zhang
A1 Olga Pletnikova
A1 Juan C. Troncoso
A1 Shelia Pirooznia
A1 Shaida A. Andrabi
A1 Valina L. Dawson
A1 Ted M. Dawson
YR 2016
UL http://www.eneuro.org/content/3/4/ENEURO.0183-16.2016.abstract
AB 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.