PGC-1s in the Spotlight with Parkinson's Disease

Int J Mol Sci. 2021 Mar 28;22(7):3487. doi: 10.3390/ijms22073487.

Abstract

Parkinson's disease is one of the most common neurodegenerative disorders worldwide, characterized by a progressive loss of dopaminergic neurons mainly localized in the substantia nigra pars compacta. In recent years, the detailed analyses of both genetic and idiopathic forms of the disease have led to a better understanding of the molecular and cellular pathways involved in PD, pointing to the centrality of mitochondrial dysfunctions in the pathogenic process. Failure of mitochondrial quality control is now considered a hallmark of the disease. The peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) family acts as a master regulator of mitochondrial biogenesis. Therefore, keeping PGC-1 level in a proper range is fundamental to guarantee functional neurons. Here we review the major findings that tightly bond PD and PGC-1s, raising important points that might lead to future investigations.

Keywords: PGC-1; Parkinson’s disease; coactivators; mitochondria; neurodegenerative disease.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA, Mitochondrial / metabolism
  • DNA-Binding Proteins / metabolism
  • Dopaminergic Neurons / metabolism
  • Genome-Wide Association Study
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Mice
  • Mitochondria / metabolism
  • Neurodegenerative Diseases / metabolism
  • Neurons / metabolism*
  • Organelle Biogenesis
  • Oxidative Stress
  • Parkinson Disease / metabolism*
  • Pars Compacta / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / physiology*
  • Phosphorylation
  • Protein Deglycase DJ-1 / metabolism
  • Protein Kinases / metabolism
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Vesicular Transport Proteins / metabolism
  • alpha-Synuclein / metabolism

Substances

  • CHCHD2 protein, human
  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • VPS35 protein, human
  • Vesicular Transport Proteins
  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • PARK7 protein, human
  • Protein Deglycase DJ-1