Mohan Maneesh, Mannan Ashi, Kakkar Chirag, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Curr Drug Targets. 2025;26(1):33-58. doi: 10.2174/0113894501320839240918110656.
Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.
Nrf2是一种参与防御机制，特别是氧化应激的关键蛋白质，它通过减轻氧化应激和炎症在神经疾病（NDs）中发挥重要作用。包括阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症、中风、癫痫、精神分裂症、抑郁症和自闭症在内的神经疾病表现出铁死亡，即由脂质和铁依赖性活性氧（ROS）积累导致的铁依赖性调节性细胞死亡。研究表明，Nrf2在调节神经疾病中的铁死亡方面发挥着关键作用。Nrf2表达及其靶基因（HO-1、Nqo-1和Trx）与年龄相关的下降与铁介导的细胞死亡增加同时出现，导致神经疾病的发生。Nrf2通过各种细胞和分子机制对铁依赖性细胞死亡和铁死亡的调节为理解这些神经疾病的病理过程提供了一条潜在的治疗途径。本综述强调了Nrf2和铁死亡在多种神经疾病中的作用机制，为未来的研究和治疗方法提供了有价值的见解。
