Glitazones, PPAR-γ and Neuroprotection

• Published in: Mini reviews in medicinal chemistry
• Main Authors: Kumar, Ashwini Prem, Prabitha P, Kumar, B R Prashantha, Jeyarani, Victoria, Dhanabal, S P, Justin, Antony
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2021
• Subjects: Neuroprotection; Glitazones; Mitochondrial biogenesis; Cytokines; Conformational changes; PPAR-γ
• ISSN: 1875-5607
• DOI: 10.2174/1389557521666210304112403

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 regulatory stable complex which 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, anti-inflammatory responses, and mitochondrial biogenesis required for neuroprotection in various neurodegenerative conditions.