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.
Keywords: PPAR-γ, glitazones, conformational changes, cytokines, mitochondrial biogenesis, neuroprotection.
Mini-Reviews in Medicinal Chemistry
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.
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Cite this article as:
Kumar Prem Ashwini , P Prabitha , Kumar Prashantha B.R., Jeyarani Victoria, Dhanabal S.P. and Justin Antony*, Glitazones, PPAR-γ and Neuroprotection, Mini-Reviews in Medicinal Chemistry 2021; 21 (12) . https://dx.doi.org/10.2174/1389557521666210304112403
DOI https://dx.doi.org/10.2174/1389557521666210304112403 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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