Sharma Veerta, Sharma Prateek, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
Metab Brain Dis. 2024 Dec 19;40(1):70. doi: 10.1007/s11011-024-01452-2.
Parkinson's disease (PD) is the neurodegenerative disorder characterized by the progressive degeneration of nigrostriatal dopaminergic neurons, leading to the range of motor and non-motor symptoms. There is mounting evidence suggesting that oxidative stress, neuroinflammation and mitochondrial dysfunction play pivotal roles in the pathogenesis of PD. Current therapies only alleviate perturbed motor symptoms. Therefore, it is essential to find out new therapies that allow us to improve not only motor symptoms, but non-motor symptoms like cognitive impairment and modulate disease progression. Nuclear factor erythroid 2-related factor 2 (Nrf2) is transcription factor that regulates the expression of numerous anti-oxidants and cytoprotective genes can counteract oxidative stress, neuroinflammation and mitochondrial dysfunction, thereby potentially ameliorating PD-associated pathology. The current review discusses about the Nrf2 structure and function with special emphasis on various molecular signalling pathways involved in positive and negative modulation of Nrf2, namely Glycogen synthase kinase-3β, Phosphoinositide-3-kinase, AMP-activated protein kinase, Mitogen activated protein kinase, nuclear factor-κB and P62. Furthermore, this review highlights the various Nrf2 activators as promising therapeutic agents for slowing down the progression of PD.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质纹状体多巴胺能神经元进行性退化，导致一系列运动和非运动症状。越来越多的证据表明，氧化应激、神经炎症和线粒体功能障碍在PD的发病机制中起关键作用。目前的治疗方法只能缓解运动症状的紊乱。因此，找到不仅能改善运动症状，还能改善认知障碍等非运动症状并调节疾病进展的新疗法至关重要。核因子红细胞2相关因子2（Nrf2）是一种转录因子，它调节许多抗氧化剂和细胞保护基因的表达，能够对抗氧化应激、神经炎症和线粒体功能障碍，从而有可能改善与PD相关的病理状况。本综述讨论了Nrf2的结构和功能，特别强调了参与Nrf2正负调节的各种分子信号通路，即糖原合酶激酶-3β、磷酸肌醇-3激酶、AMP激活的蛋白激酶、丝裂原活化蛋白激酶、核因子-κB和P62。此外，本综述强调了各种Nrf2激活剂作为减缓PD进展的有前景的治疗药物。
