Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan 6718773654, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan 6718773654, Iran.
CNS Neurol Disord Drug Targets. 2023;22(10):1453-1461. doi: 10.2174/1871527322666221005122408.
Parkinson's disease (PD) is a chronic and progressive neurological disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). The pathogenesis of PD is strongly related to mitochondrial dysfunction, oxidative stress, and neuroinflammation. This indicates that PD can be treated with anti-oxidative substitutes and anti-inflammatory compounds. The neuroprotective and anti-inflammatory effects of peroxisome proliferator-activated receptor γ (PPAR-γ) agonists decrease cell death and halt the increase in neurodegeneration, which is why they have been given a lot of importance in research. Antidiabetic and anti-inflammatory effects have been observed to be generated by pioglitazone (PG), a selective peroxisome proliferator-activated receptor γ (PPAR-γ) agonist that regulates neural plasticity in various neurodegenerative disorders. The neuroprotective and anti-inflammatory effects of PG are assessed in this article. It was found that the patients with DM who received PG treatment were noticeably at a lower risk of PD. However, some clinical studies have not proven a strong link between the therapeutic effects of PG on PD. As per suggestions of preclinical studies, the therapeutic effects of PG treatment include; increased life expectancy of neurons, decreased oxidative stress, halted microglial activity, lower inflammation (reduced NF-κB, COX-2, and iNOS), reduced mitochondrial dysfunction, rise in motor function (motor agility) and non-motor function (lowered cognitive dysfunction). In conclusion, we determined that PG exerts neuroprotective and anti-inflammatory effects in PD models and it can be considered a potential therapeutic candidate for PD.
帕金森病（PD）是一种慢性进行性神经退行性疾病，其特征是黑质致密部（SNc）中的多巴胺能神经元退化。PD 的发病机制与线粒体功能障碍、氧化应激和神经炎症密切相关。这表明 PD 可以用抗氧化替代物和抗炎化合物治疗。过氧化物酶体增殖物激活受体 γ（PPAR-γ）激动剂的神经保护和抗炎作用可减少细胞死亡并阻止神经退行性变的增加，这就是为什么它们在研究中受到高度重视的原因。已经观察到吡格列酮（PG）具有抗糖尿病和抗炎作用，PG 是一种选择性过氧化物酶体增殖物激活受体 γ（PPAR-γ）激动剂，可调节各种神经退行性疾病中的神经可塑性。本文评估了 PG 的神经保护和抗炎作用。结果发现，接受 PG 治疗的糖尿病患者患 PD 的风险明显降低。然而，一些临床研究并未证明 PG 对 PD 的治疗效果之间存在很强的联系。根据临床前研究的建议，PG 治疗的治疗效果包括：神经元预期寿命延长，氧化应激减少，小胶质细胞活性停止，炎症减轻（NF-κB、COX-2 和 iNOS 降低），线粒体功能障碍减轻，运动功能（运动敏捷性）和非运动功能（认知功能障碍降低）提高。总之，我们确定 PG 在 PD 模型中具有神经保护和抗炎作用，可被视为 PD 的潜在治疗候选药物。
