Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Sciences and Technology, Gamasa, 7730103, Egypt.
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh, 11597, Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Neuropharmacology. 2024 Jun 1;250:109909. doi: 10.1016/j.neuropharm.2024.109909. Epub 2024 Mar 15.
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-κB 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.
帕金森病（PD）是一种常见的神经退行性疾病，其特征为运动和心理功能障碍。姑息治疗和多巴胺补充疗法是目前仅有的两种治疗选择。钙通道阻滞剂（CCB）已被报道可预防多种神经退行性疾病。本研究旨在评估非洛地平（10mg/kg，口服）作为 CCB 对实验性诱导的 PD 相关运动和生化功能障碍的神经保护作用，使用鱼藤酮（2.5mg/kg，IP）并探讨其潜在机制。鱼藤酮诱导的神经运动损伤结果与 PD 相关，纹状体中氧化应激增加，NO 水平升高，抗氧化能力降低。Nrf2 含量显著降低，黑质和纹状体中的α-突触核蛋白和 tau 蛋白积累。这些观察结果在非洛地平治疗后明显改善。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，这一点得到了炎症抑制和纹状体 NF-κB 和 TNF-α含量显著降低的证实。此外，非洛地平增强了线粒体自噬，这一点通过线粒体 Parkin 的显著增加和 LC3a/b 和 SQSTM1/p62 的抑制得到证实。总之，非洛地平恢复了多巴胺的合成，减轻了氧化应激、炎症和线粒体功能障碍，并改善了与 PD 相关的运动障碍的自噬过程。
