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.

转录因子 PPAR-γ 属于核受体家族，已成为多种神经退行性疾病和代谢紊乱的潜在治疗靶点。有趣的是，据报道 PPAR-γ 通过上调其转录共激活因子 PGC-1α 并随后调节多个分子事件，在各种慢性神经系统疾病中具有有益作用。虽然有几个因素导致神经退行性疾病的进展，但 PGC-1α 表达的功能障碍主要与主要神经退行性疾病的发病机制相关。这篇综述揭示了格列酮对 PPAR-γ 的配体依赖性激活可以引发二级蛋白质的结构构象变化，因此招募 PGC-1α 形成稳定的调节复合物，阻碍导致神经变性的各种分子途径。本综述中包含的初步计算机研究的有希望的结果支持 PPAR-γ 依赖性激活中枢 PGC-1α 信号的新型格列酮是一种令人鼓舞的策略，可增强氧自由基解毒系统、抗炎反应和线粒体生物发生所需的在各种神经退行性疾病中的神经保护作用。