Glitazones, PPAR-γ and Neuroprotection

Author(s): Ashwini Prem Kumar, Prabitha P, B.R. Prashantha Kumar, Victoria Jeyarani, S.P. Dhanabal, Antony Justin*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 21 , Issue 12 , 2021


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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.

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Article Details

VOLUME: 21
ISSUE: 12
Year: 2021
Published on: 02 July, 2021
Page: [1457 - 1464]
Pages: 8
DOI: 10.2174/1389557521666210304112403
Price: $65

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