Adult conditional knockout of PGC-1α leads to loss of dopamine neurons

Academic Article


  • 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.
  • Published In

  • eNeuro  Journal
  • Digital Object Identifier (doi)

    Author List

  • Jiang H; Kang SU; Zhang S; Karuppagounder S; Xu J; Lee YK; Kang BG; Lee Y; Zhang J; Pletnikova O
  • Volume

  • 3
  • Issue

  • 4