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.
Drew
Paul D
PD
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. drewpauld @uams.edu
Xu
Jihong
J
Storer
Paul D
PD
Chavis
Janet A
JA
Racke
Michael K
MK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D047492:Peroxisome Proliferator-Activated Receptors