Neuroprotective Mechanisms of PPAR delta: Modulation of Oxidative Stress and Inflammatory Processes

Peroxisome proliferator-activated receptors (PPAR alpha, delta, and gamma) are ligand-activated transcription factors that regulate a wide range of cellular processes, including inflammation, proliferation, differentiation, metabolism, and energy homeostasis. All three PPAR subtypes have been identified in the central nervous system (CNS) of rodents. While PPAR alpha and PPAR gamma are expressed in more restricted areas of the CNS, PPAR delta is ubiquitously expressed and is the predominant subtype. Although data regarding PPAR delta are limited, studies have demonstrated that administration of PPAR delta agonists confers neuroprotection following various acute and chronic injuries to the CNS, such as stroke, multiple sclerosis, and Alzheimer's disease. The antioxidant and anti-inflammatory properties of PPAR delta agonists are thought to underly their neuroprotective efficacy. This review will focus on the putative neuroprotective benefits of therapeutically targeting PPAR delta in the CNS, and specifically, highlight the antioxidant and anti-inflammatory functions of PPAR delta agonists.