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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.

Objectives This study is designed to evaluate the role of tuberoinfundibular peptide of 39 (TIP39) in connection with glucocorticoid receptor‐mediated glutamate/GABA abnormalities in chronic unpredictable mild stress (CUMS) model. Methods Male Sprague–Dawley rats were treated with TIP39 (1 and 10 nmol, i.c.v) and diazepam 2 mg/kg throughout the stress period (28 days) in alternate days. Then, rats were subjected for different behavioural activity followed by biochemical, gene expression and histological examinations. Key findings Chronic unpredictable mild stress rats showed significant cognitive impairment in Morris water maze, Novel object recognition and Y maze test. This was reversed after TIP39 administration. Moreover, TIP39 significantly decreased the brain glutamate and acetyl cholinesterase levels in CUMS rats, whereas it increases the level of GABA after TIP39 treatment. These changes were evident with increased glutamic acid decarboxylase enzyme activity by TIP39. TIP39 significantly decreased the brain glucocorticoid and mineralocorticoid receptor expression ratio in comparison with CUMS rats. Moreover, histological abnormalities in prefrontal cortex and hippocampus were markedly improved after TIP39 administration in CUMS rats. Conclusions Tuberoinfundibular peptide of 39 can be a potent neuroendocrine modulator in treating cognitive impairment induced by CUMS rats by controlling glucocorticoid receptor‐mediated glutamate/GABA abnormalities in brain.

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.

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