The Strategy of Targeting Peroxisome Proliferator-Activated Receptor (PPAR) in the Treatment of Neuropsychiatric Disorders

Adv Exp Med Biol. 2023;1411:513-535. doi: 10.1007/978-981-19-7376-5_22.ABSTRACTPeroxisome proliferator-activated receptors (PPARs) are nonsteroid nuclear receptors and transcription factors that regulate several neuroinflammatory and metabolic processes, recently involved in several neuropsychiatric conditions, including Alzheimer's disease, Parkinson's disease, major depressive disorder, post-traumatic stress disorder (PTSD), schizophrenia spectrum disorders, and autism spectrum disorders. PPARs are ligand-activated receptors that, following stimulation, induce neuroprotective effects by decreasing neuroinflammatory processes through inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) expression and consequent suppression of pro-inflammatory cytokine production. PPARs heterodimerize with the retinoid X-receptor (RXR) and bind to PPAR-responsive regulatory elements (PPRE) in the promoter region of target genes involved in lipid metabolism, synthesis of cholesterol, catabolism of amino acids, and inflammation. Interestingly, PPARs are considered functionally part of the extended endocannabinoid (eCB) system that includes the classic eCB, anandamide, which act at cannabinoid receptor types 1 (CB1) and 2 (CB2) and are implicated in the pathophysiology of stress-related neuropsychiatric disorders. In preclinical studies, PPAR stimulation improves anxiety and depression-like behaviors by enhancing neurosteroid biosynthesis. The peculiar functio...
Source: Advances in Experimental Medicine and Biology - Category: Research Authors: Source Type: research