Regulation of Glial Cell Functions by PPAR‐γ Natural and Synthetic Agonists

Abstract

In the recent years, the peroxisome proliferator-activated receptor-γ (PPAR-γ), 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-γ agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Δ12,14 prostaglandin J2), 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-γ 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-γ 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.

Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury

“…It is generally believed that glial cells contribute to hypersensitivity in chronic pain conditions; spinal microglia and astrocytes play a major role in the development and maintenance of allodynia, respectively (1). Both types of activated glia express PPARγ in cultures and in injured brain (9). In addition, thiazolidinedione derivatives, including pioglitazone, were reported to inhibit induction of inflammatory mediators in lipopolysaccharide-stimulated astrocyte cultures and microglia cultures (10).…”

Microglial Activation in Stroke: Therapeutic Targets

“…165 The primary endogenous ligand for PPAR␥ is 15-deoxy-prostaglandin J 2 (15d-PGJ2), and several synthetic ligands such as thiazolidinedione have now been generated. PPAR␥ expression in healthy brain is most prominent in glial cells, 166 but occurs also in neurons. 167,168 PPAR␥ expression in primary microglia cells is downregulated upon microglial activation, but introduction of the natural ligand, 15d-PGJ2, restores PPAR␥ expression and PPAR␥ DNA binding.…”

The Pleiotropic Effects of Curcumin.

“…[48] This could be explained by the anti inflammatory action of curcumin, which is a PPAR-γ agonist. [49] Many ocular inflammatory diseases are mediated by immune cells such as microglia and the anti inflammatory action of PPAR-γ may be effective in these conditions [50].…”

“…[38] ( NF-κB is raised in intestinal biopsies of IBD patients) [39] Cardiovascular system(Nanocurcumin) conserves mitochondrial function, under hypoxic conditions [44] Bronchial asthma Reduce arachidonic acid release by suppressing cytosolic phospholipase A2 phosphorylation [47] uveitis anti inflammatory action of curcumin [48] PPAR-γ agonistic action-anti inflammatory property. [49,50] depression inhibit MAO A in mouse brain [53] interacting with serotonergic receptors [54] …”