Current Progress on Peroxisome Proliferator-activated Receptor Gamma Agonist as an Emerging Therapeutic Approach for the Treatment of Alzheimer's Disease: An Update

Author(s): Mahmood Ahmad Khan*, Qamre Alam, Absarul Haque, Mohammad Ashafaq, Mohd Jahir Khan, Ghulam Md Ashraf*, Mahboob Ahmad.

Journal Name: Current Neuropharmacology

Volume 17 , Issue 3 , 2019

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Graphical Abstract:


Abstract:

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder, characterized by the deposition of amyloid-β within the brain parenchyma resulting in a significant decline in cognitive functions. The pathophysiological conditions of the disease are recognized by the perturbation of synaptic function, energy and lipid metabolism. In Addition deposition of amyloid plaques also triggers inflammation upon the induction of microglia. Peroxisome proliferatoractivated receptors (PPARs) are ligand-activated transcription factors known to play important role in the regulation of glucose absorption, homeostasis of lipid metabolism and are further known to involved in repressing the expression of genes related to inflammation. Therefore, agonists of this receptor represent an attractive therapeutic target for AD. Recently, both clinical and preclinical studies showed that use of Peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves both learning and memory along with other AD related pathology. Thus, PPARγ signifies a significant new therapeutic target in treating AD. In this review, we have shed some light on the recent progress of how, PPARγ agonist selectively modulated different cellular targets in AD and its amazing potential in the treatment of AD.

Keywords: Alzheimer's disease, Peroxisome proliferator-activated receptors, Transactivation, β-amyloid, Thiazolidinedione, Insulin sensitivity, Rosiglitazone, Blood-brain-barrier.

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VOLUME: 17
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Year: 2019
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