Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, belonging to the nuclear receptor family, which has high expression of three structurally homologous PPARs isotypes (PPARα, PPARβ/δ, and PPARγ) in brain. Several studies have discovered role of PPARs in oxidative stress, mitochondrial dysfunction, neuroinflammation and production of the toxic proteins in various neurodegenerative disorders such as Parkinson disease, Alzheimer’s disease, Huntington disease, Amyotrophic Lateral Sclerosis, Multiple sclerosis etc. Currently available drugs provide symptomatic relief, but disease progression cannot be stopped, because of their unclear molecular approach. The ability of PPAR to modulate the pathways involved in these conditions paved a path for future studies. Due to increasing challenges to treat central nervous system related disorders, hence PPARs have attracted much attention nowadays. In this review, we discussed various mechanisms of PPARs subtypes in neurodegenerative disorders. We congregate the molecular evidences which support PPARs as a therapeutic target to treat neurodegenerative disorders from preclinical and clinical studies and provide a basis for the potential therapeutic use of PPAR ligands in human diseases.
Pentacyclic Phytomolecule 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) from Frankincense family has proven for the neuroprotection and recognized as an orphan drug for the treatment of cerebral edema. Nonetheless, AKBA have promising indications with Peroxisome proliferator activated receptor gamma (PPARγ) associated to cognitive function not deliberated so far. In order to substantiate the potential role of AKBA on memory function, we examine the contribution of PPARγ activation and its downstream process. Modified method of scopolamine induced dementia rats were treated with AKBA (5, 10&15 mg/kg,i.p) and Donepezil (2.5 mg/kg,i.p). Scopolamine induced short term spatial, working memory and recognition memory impairment was reversed significantly after AKBA treatment. AKBA administration diminished the Acetylcholine esterase (AchE) activity and preserved brain GABA and glutamate mediated neuronal excitability. Further, gene expression study reveals AKBA ameliorates the memory impairment via activating PPARγ and its downstream regulators, matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) genes in hippocampus. This study concludes that the treatment with AKBA can be a novel Phyto-molecule of interest for treating dementia via up-regulating hippocampus genes mediated cholinergic activation.
The foremost important risk factor for depression is stress. All kind of stresses are vulnerable to the hypothalamic pituitary adrenal (HPA) axis and promote the paraventricular nucleus (PVN) that releases corticotropin releasing factor (CRF) in the hypothalamus, which stimulates corticosterone (CORT) release. 1 Overt corticosteroid release can cause the energy metabolism, neuronal plasticity, excitability and neuroendocrine regulation in both central and peripheral regions to be mediated by Glucocorticoid
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