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
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/stroke
Ischemic 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-1
PPARγ ligands reduce the infarct size in animal models