PGC-1α sparks the fire of neuroprotection against neurodegenerative disorders

Ageing Res Rev. 2018 Jul:44:8-21. doi: 10.1016/j.arr.2018.03.004. Epub 2018 Mar 23.

Abstract

Recently, growing evidence has demonstrated that peroxisome proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a superior transcriptional regulator that acts via controlling the expression of anti-oxidant enzymes and uncoupling proteins and inducing mitochondrial biogenesis, which plays a beneficial part in the central nervous system (CNS). Given the significance of PGC-1α, we summarize the current literature on the molecular mechanisms and roles of PGC-1α in the CNS. Thus, in this review, we first briefly introduce the basic characteristics regarding PGC-1α. We then depict some of its important cerebral functions and discuss upstream modulators, partners, and downstream effectors of the PGC-1α signaling pathway. Finally, we highlight recent progress in research on the involvement of PGC-1α in certain major neurodegenerative disorders (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Collectively, the data presented here may be useful for supporting the future potential of PGC-1α as a therapeutic target.

Keywords: Cerebrum functions; Neurodegenerative disorders; Peroxisome proliferator activated receptor γ coactivator-1α; Signaling pathway.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Gene Expression Regulation
  • Humans
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism*
  • Neuroprotection / physiology*
  • Parkinson Disease / diagnosis
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / biosynthesis*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology
  • Transcription Factors / metabolism

Substances

  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Reactive Oxygen Species
  • Transcription Factors