Peroxisome Proliferator-Activated Receptor Delta (PPARδ) as a Metabolic Gatekeeper of Cerebrovascular Integrity

The peroxisome proliferator-activated receptor delta (PPARδ) is a nuclear receptor highly expressed in vasculature and serves a central role in coordinating vascular and metabolic homeostasis across multiple physiological systems. Recent studies have highlighted PPARδ's remarkable ability to regulate endothelial fatty acid oxidation, enhance metabolic flexibility, and modulate angiogenic responses critical for vascular adaptation and repair. Beyond its metabolic functions, PPARδ orchestrates multiple protective pathways that preserve cerebrovascular homeostasis, including endothelial repair, maintenance of blood-brain barrier integrity, mitochondrial biogenesis, and stability of the neurovascular unit, collectively enhancing endothelial resilience to stress. Dysregulation of PPARδ signaling has been implicated in various vascular and neurodegenerative disease states, underscoring its clinical relevance. In this literature review, we synthesize current findings on PPARδ-mediated signaling pathways and evaluate its potential as a promising therapeutic target. We further explore mechanistic roles across pathological contexts, as well as discuss emerging translational strategies aimed at harnessing PPARδ modulation for vascular and neuroprotective therapies.