Glitazones, PPAR-γ and Neuroprotection.

Ashwini Prem Kumar, Prabitha P, B R Prashantha Kumar, Victoria Jeyarani, S P Dhanabal, Antony Justin

Mini reviews in medicinal chemistry 2021

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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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Ashwini Prem Kumar, Prabitha P, B R Prashantha Kumar, Victoria Jeyarani, S P Dhanabal, Antony Justin. Glitazones, PPAR-γ and Neuroprotection. Mini reviews in medicinal chemistry. 2021;21(12):1457-1464