In the recent years, the
peroxisome proliferator-activated receptor-gamma (
PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative
brain disorders.
PPAR-gamma agonists, which include naturally occurring compounds (such as long chain
fatty acids and the
cyclopentenone prostaglandin 15-deoxy Delta(12,14)
prostaglandin J(2)), and synthetic agonists (among which the
thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases,
amyotrophic lateral sclerosis,
multiple sclerosis and
stroke, as well as in few clinical studies. The pleiotropic effects of
PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for
PPAR-gamma agonists in controlling
neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in
brain inflammation.