PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease

Title:PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease

Volume: 20 Issue: 8

Author(s): Mohit Kumar, Anita Ashok Sharma, Ashok Kumar Datusalia and Gopal L. Khatik*

Affiliation:

• Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli, Uttar Pradesh, 226002, India

Abstract:

Alzheimer's disease (AD) is a neurodegenerative disease leading to dementia because of complex phathomechanisms like amyloid β (Aβ) aggregation, tau aggregates, and neurofibrillary tangles. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported recently with neuroprotective and anti-inflammatory properties. PPARs belong to the superfamily of nuclear hormone receptors and function as ligand-activated transcription factors. These have emerged as crucial players in the pathogenesis of AD. This review presented the potential of PPARs and their agonists in treating neurodegenerative diseases like AD.

PPARs regulate the expression of specific genes vital for synaptic function and neurotransmitter release. PPAR agonists play a critical role in increasing the clearance of Aβ peptides by lowdensity lipoprotein receptor-related protein 1 (LRP1) in the microvascular endothelial cells of the human brain. Studies have shown that PPAR agonists reduce the level of APoE-mRNA, contributing to the accumulation of Aβ plaques and up-regulation of PPAR. A knockout of miR-128 has been found to inhibit AD-like cognitive decline, amyloid precursor protein (APP) amyloidogenic processing, and inflammatory responses in AD.

PPARs are involved in the pathomechanism of AD, and therefore, PPAR agonists could be viable options for controlling the neurodegenerative symptoms and may be useful in treating AD.

Cite this article as:

Kumar Mohit, Sharma Ashok Anita, Datusalia Kumar Ashok and Khatik L. Gopal*, PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease, Medicinal Chemistry 2024; 20 (8) . https://dx.doi.org/10.2174/0115734064295063240422100615