Title:Glitazones, PPAR-γ and Neuroprotection
Volume: 21
Issue: 12
Author(s): Ashwini Prem Kumar, Prabitha P, B.R. Prashantha Kumar, Victoria Jeyarani, S.P. Dhanabal and Antony Justin*
Affiliation:
- Department of Pharmacology, JSS College of Pharmacy, Ooty-643001, Tamilnadu,India
Keywords:
PPAR-γ, glitazones, conformational changes, cytokines, mitochondrial biogenesis, neuroprotection.
Abstract: The transcriptional factor PPAR-γ belongs to the nuclear receptor family, which has become
a potential therapeutic target for several neurodegenerative diseases and metabolic disorders.
Interestingly, PPAR-γ has been reported to have beneficial effects in various chronic neurological
conditions via upregulation of its transcriptional co-activator PGC-1α and followed by regulation of
multiple molecular events. Although several factors contribute to the progression of neurodegeneration,
the dysfunction of PGC-1α expression is primarily interlinked with the pathogenesis of major
neurodegenerative diseases. This review gives an insight that ligand-dependent activation of PPAR-γ
by glitazones could initiate the structural conformational changes of the secondary proteins, thus recruiting
the PGC-1α to form a stable regulatory complex that hampers the various molecular pathways
contributing to neurodegeneration. The promising outcomes of the preliminary in silico studies included
in this review support that PPAR-γ dependent activation of central PGC-1α signaling by novel
glitazones is an encouraging strategy to enhance the oxy-radicals detoxifying system, antiinflammatory
responses, and mitochondrial biogenesis required for neuroprotection in various neurodegenerative
conditions.