Parkinson's disease (PD) is a prevalent neurodegenerative disorder, characterized by motor and psychological dysfunction. Palliative treatment and dopamine replenishment therapy are the only available therapeutic options. Calcium channel blockers (CCBs) have been reported to protect against several neurodegenerative disorders. The current study was designed to evaluate the neuroprotective impact of Felodipine (10 mg/kg, orally) as a CCB on motor and biochemical dysfunction associated with experimentally induced PD using rotenone (2.5 mg/kg, IP) and to investigate the underlying mechanisms. Rotenone induced deleterious neuromotor outcomes, typical of those associated with PD. The striatum revealed increased oxidative burden and NO levels with decreased antioxidant capacity. Nrf2 content significantly decreased with the accumulation of α-synuclein and tau proteins in both the substantia nigra and striatum. These observations significantly improved with felodipine treatment. Of note, felodipine increased dopamine levels in the substantia nigra and striatum as confirmed by the suppression of inflammation and the significant reduction in striatal NF-B and TNF-α contents. Moreover, felodipine enhanced mitophagy, as confirmed by a significant increase in mitochondrial Parkin and suppression of LC3a/b and SQSTM1/p62. In conclusion, felodipine restored dopamine synthesis, attenuated oxidative stress, inflammation, and mitochondrial dysfunction, and improved the mitophagy process resulting in improved PD-associated motor impairment.

中文翻译：

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非洛地平对实验诱发的帕金森病的神经调节作用：PINK1-Parkin 线粒体自噬途径的可能贡献

帕金森病（PD）是一种常见的神经退行性疾病，其特征是运动和心理功能障碍。姑息治疗和多巴胺补充疗法是唯一可用的治疗选择。据报道，钙通道阻滞剂（CCB）可以预防多种神经退行性疾病。目前的研究旨在评估非洛地平（10 mg/kg，口服）作为 CCB 对与使用鱼藤酮（2.5 mg/kg，IP）实验诱导的 PD 相关的运动和生化功能障碍的神经保护作用，并调查其潜在机制。鱼藤酮会引起有害的神经运动结果，这是与帕金森病相关的典型症状。纹状体显示氧化负担和一氧化氮水平增加，抗氧化能力下降。随着黑质和纹状体中 α-突触核蛋白和 tau 蛋白的积累，Nrf2 含量显着降低。非洛地平治疗后这些观察结果显着改善。值得注意的是，非洛地平增加了黑质和纹状体中的多巴胺水平，这通过抑制炎症以及纹状体 NF-B 和 TNF-α 含量的显着降低得到证实。此外，非洛地平增强了线粒体自噬，线粒体 Parkin 显着增加以及 LC3a/b 和 SQSTM1/p62 抑制证实了这一点。总之，非洛地平恢复了多巴胺合成，减轻了氧化应激、炎症和线粒体功能障碍，并改善了线粒体自噬过程，从而改善了 PD 相关的运动障碍。