Peroxisome proliferator-activated receptor-γ cofactors in neurodegeneration

IUBMB Life. 2012 Dec;64(12):958-64. doi: 10.1002/iub.1097. Epub 2012 Nov 6.

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) was initially involved in the regulation of glucose and lipid metabolism, cell differentiation, as well as in the transcriptional control of a wide range of inflammatory genes. However, during the last decade, there has been evidence of the implication of this nuclear receptor in neurodegeneration. Various studies have shown that the administration of PPARγ ligands leads to a reduced pathology in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, and stroke. PPARγ cofactors have a critical function in regulating the activity of PPARγ. Recent reports have brought to light the role of the PPARγ coactivator-1α (PGC-1α) in several neurodegenerative pathologies. However, very little is know about other PPARγ cofactors in the brain, such as the receptor-interacting protein 140, as well as the nuclear receptor corepressor, which seems to be required for normal neural development at specific embryonic stages. In this review, we aim to analyze the role of the main regulators of PPARγ in the brain and during neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Co-Repressor Proteins / genetics
  • Co-Repressor Proteins / metabolism*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Mice
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Interacting Protein 1
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • Adaptor Proteins, Signal Transducing
  • Co-Repressor Proteins
  • Heat-Shock Proteins
  • Nuclear Proteins
  • Nuclear Receptor Interacting Protein 1
  • PPAR gamma
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors