PPARδ in neurological diseases: Mechanisms and therapeutic prospects

Peroxisome proliferator-activated receptors (PPARs) are a class of nuclear receptors that play a pivotal role in diverse physiological processes, including lipid metabolism, energy homeostasis, and immune responses, through the regulation of gene expression. Among the PPAR subtypes, PPARδ (also referred to as PPARβ/δ) has garnered growing attention in the research of neurological disorders, attributed to the recent discovery of its high expression level in the nervous system. Accumulating evidence demonstrates that PPARδ exerts multiple beneficial effects, such as inhibiting neuroinflammation, enhancing mitochondrial function, maintaining cellular energy balance, and exerting neuroprotective activities. Neurological diseases, encompassing neurodegenerative disorders, cerebrovascular diseases, and neuroinflammatory conditions, impose a substantial burden on global health. The purpose of this review is to summarize the latest research advances in PPARδ, analyze and delineate the specific molecular mechanisms underlying its protective effects against neurological diseases, and discuss the current challenges and future prospects in this field, thereby providing a theoretical basis for the development of novel therapeutic strategies. Additionally, this review highlights several compounds and PPARδ-targeted drug development strategies that have been investigated for ameliorating the pathological progression of these neurological disorders.