Peroxisome proliferator-activated receptor agonist regulation of glial activation: Relevance to CNS inflammatory disorders

Peroxisome proliferator-activated receptors (PPARs) play key roles in lipid metabolism and inflammation. Recent studies indicated that PPARs are also capable of modulating immune responses. Microglia and astrocytes are cells resident to the central nervous system (CNS) that function to protect against environmental insults including pathogens. However, following CNS inflammation, reactive gliosis occurs which is characterized by astrocyte hypertrophy and increased glial proliferation. Under such conditions, glia can become chronically activated and may contribute to the neuropathology associated with a variety of neuroinflammatory disorders including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and stroke. A review of the role of PPAR agonists in modulating glial cell activation is presented. Included is a discussion of the molecular mechanisms of action of these PPAR agonists and the potential utility of these agents for the treatment of neuroinflammatory disorders.