Peroxisome proliferator-activated receptor-γ cofactors in neurodegeneration

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.