Review Article

PPAR Regulation of Inflammatory Signaling in CNS Diseases

Table 1

Role of PPARs in the regulation of neuroinflammatory diseases.

CNS disease Inflammatory response Effect of PPAR agonists

Multiple sclerosis Activation of macrophage, microglia and dendritic cells; infiltration of Th1/Th17 cells in the CNS; induction of NF-κB and Jak-Stat pathway and release of IL-12, IFNγ, IL-17 and other cytokines in the CNS PPARα, δ and γ agonists ameliorate EAE by inhibiting inflammation
Alzheimer’s disease Beta-amyloid (Aβ) accumulation leads to CNS inflammation via TNFα and NF-κB pathway and secretion of inflammatory cytokines PPARγ ligands reduce neuronal loss in animal models of AD
Infection During bacterial, viral, fungal and parasitic infection, activated APC and T cells release TNFα, IFNγ, iNOS, IL-2, IL-6 and induce inflammation via NF-κB, Stat and AP-1 signaling pathways PPAR agonists regulate infection associated inflammation
Trauma CNS injury results in the activation of resident microglia and astrocytes resulting inflammation through secretion of TNFα, prostaglandin and COX-2 and mediate inflammation via NF-κB, Stat1 and AP-1 pathways PPARα, δ and γ ligands regulate inflammatory response in trauma
Ischemia/strokeIschemic stroke associates with recruitment and activation of macrophages and neutrophils via increased expression of VCAM-1, ICAM-1, IL-6, IL-8 and COX-2 through Stat-1PPARγ ligands reduce the infarct size in animal models