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, 2008, 864140

Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists


Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists

Antonietta Bernardo et al. PPAR Res.


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.


Figure 1
Figure 1
Cellular targets of PPAR-γ agonists in neurodegenerative diseases. PPAR-γ agonists can control neuroinflammation, neurodegeneration, and demyelination by effecting several cellular targets and by several direct and indirect mechanisms. PPAR-γ agonists can control glial activation, preventing a number of proinflammatory activities that can contribute to myelin/OL damage and neurotoxicity PPAR-γ agonists may also affect OLs and neurons, by preventing release inflammatory mediators and/or promote the synthesis of soluble factors or membrane-bound molecules that control glial activation.
Figure 2
Figure 2
PPAR-γ expression in culture rat oligodendrocytes and in white matter (postnatal day 19) in rat model of global perinatal asphyxia. (a) Immunocytochemistry of rat OL progenitor cultures, prepared as previously described [40] for PPAR-γ (upper panel) and the OL marker O4 (lower panel). (b) Western blot analysis of white matter homogenates from rats at postnatal day 19 subjected to 20 minutes of perinatal asphyxia (hypoxic) and from controls, prepared as described in Piscopo et al. [48]. Inset show the decreased levels of MBP in hypoxic rats at pnd 19.

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