Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Curr Drug Targets. 2013 Jun;14(7):743-51. doi: 10.2174/1389450111314070004.
Parkinson's disease (PD) is amongst the most frequent neurodegenerative disorders, the main pathologic hallmark of which is the degeneration of the substantia nigra pars compacta. Damage to multiple cellular components, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, and proteasomal dysfunction, contribute to the progression of the neurodegenerative process. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, mainly thiazolidinediones, pioglitazone and rosiglitazone, have been successfully tested for their neuroprotective potential in PD experimental models, although the cellular target and underlying mechanism are currently a matter of debate. While the anti-inflammatory activity and attenuation of microgliosis have been proposed as a main mechanism of neuroprotection, other cellular targets might be involved, such as mitochondrial proteins controlling cellular bioenergetic and oxidative stress. Here, the current evidence of neuroprotection by PPAR-γ agonists in in vitro and in vivo experimental PD models is reported. Moreover, cellular pathways which have been investigated as potential targets of neuroprotection are reviewed. Taken together, the available data suggest that simultaneous targeting of multiple dysfunctional pathways may underlie the potent neuroprotective activity displayed by PPAR-γ agonists.
帕金森病（PD）是最常见的神经退行性疾病之一，其主要病理特征是黑质致密部的退化。多种细胞成分的损伤，如线粒体功能障碍、氧化应激、神经炎症和蛋白酶体功能障碍，导致神经退行性过程的进展。过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂，主要是噻唑烷二酮类、吡格列酮和罗格列酮，已在 PD 实验模型中成功测试了其神经保护潜力，尽管细胞靶点和潜在机制目前仍存在争议。虽然抗炎活性和小胶质细胞减少被认为是神经保护的主要机制，但其他细胞靶点也可能参与其中，如控制细胞生物能量和氧化应激的线粒体蛋白。本文报告了 PPAR-γ 激动剂在体外和体内实验性 PD 模型中的神经保护作用的最新证据。此外，还综述了作为神经保护潜在靶点的细胞途径。综上所述，现有数据表明，同时针对多个功能失调的途径可能是 PPAR-γ 激动剂显示出强大的神经保护活性的基础。
