Title:Advances in PPARs Molecular Dynamics and Glitazones as a Repurposing
Therapeutic Strategy through Mitochondrial Redox Dynamics against
Neurodegeneration
Volume: 20
Issue: 5
Author(s): Priya Durai, Narasimha M. Beeraka, Hemanth Vikram Poola Ramachandrappa, Prakash Krishnan, Pranesh Gudur, Nulgumnalli Manjunathaiah Raghavendra and Prashantha Kumar Bommenahally Ravanappa*
Affiliation:
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru 570 015, India and JSS Academy of
Higher Education & Research, Mysuru, Karnataka, India
Keywords:
PPARs, glitazones, neurodegeneration, mitochondrial dynamics, neuroinflammation, Alzheimer’s disease.
Abstract: Peroxisome proliferator-activated receptors (PPARs) activity has significant implications
for the development of novel therapeutic modalities against neurodegenerative diseases. Although
PPAR-α, PPAR-β/δ, and PPAR-γ nuclear receptor expressions are significantly reported in the
brain, their implications in brain physiology and other neurodegenerative diseases still require extensive
studies. PPAR signaling can modulate various cell signaling mechanisms involved in the
cells contributing to on- and off-target actions selectively to promote therapeutic effects as well as
the adverse effects of PPAR ligands. Both natural and synthetic ligands for the PPARα, PPARγ, and
PPARβ/δ have been reported. PPARα (WY 14.643) and PPARγ agonists can confer neuroprotection
by modulating mitochondrial dynamics through the redox system. The pharmacological effect of
these agonists may deliver effective clinical responses by protecting vulnerable neurons from Aβ
toxicity in Alzheimer’s disease (AD) patients. Therefore, the current review delineated the ligands’
interaction with 3D-PPARs to modulate neuroprotection, and also deciphered the efficacy of numerous
drugs, viz. Aβ aggregation inhibitors, vaccines, and γ-secretase inhibitors against AD; this
review elucidated the role of PPAR and their receptor isoforms in neural systems, and neurodegeneration
in human beings. Further, we have substantially discussed the efficacy of PPREs as potent
transcription factors in the brain, and the role of PPAR agonists in neurotransmission, PPAR gamma
coactivator-1α (PGC-1α) and mitochondrial dynamics in neuroprotection during AD conditions.
This review concludes with the statement that the development of novel PPARs agonists may benefit
patients with neurodegeneration, mainly AD patients, which may help mitigate the pathophysiology
of dementia, subsequently improving overall the patient’s quality of life.
