Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.

IF 3 4区医学 Q2 PHARMACOLOGY & PHARMACY Current drug targets Pub Date : 2024-09-27 DOI:10.2174/0113894501320839240918110656

Maneesh Mohan, Ashi Mannan, Chirag Kakkar, Thakur Gurjeet Singh

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Abstract

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.

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Nrf2 和铁氧化酶：探索神经系统疾病治疗方法的转化途径。

Nrf2 是一种参与防御机制（尤其是氧化应激）的重要蛋白质，它通过减少氧化应激和炎症在神经系统疾病（NDs）中发挥着重要作用。包括阿尔茨海默氏症、帕金森氏症、亨廷顿氏症、肌萎缩性脊髓侧索硬化症、中风、癫痫、精神分裂症、抑郁症和自闭症在内的 NDs 都表现出铁凋亡，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 NDs 中的铁氧化过程中发挥着关键作用。与年龄相关的 Nrf2 表达及其靶基因（HO-1、Nqo-1 和 Trx）的减少与铁介导的细胞死亡增加同时发生，从而导致 ND 发病。Nrf2 通过各种细胞和分子机制调节铁依赖性细胞死亡和铁突变，为了解这些 ND 的病理过程提供了潜在的治疗途径。本综述强调了 Nrf2 和铁突变在多种 ND 中的机制作用，为未来的研究和治疗方法提供了宝贵的见解。

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来源期刊

Current drug targets 医学-药学

CiteScore

6.20

自引率

0.00%

发文量

127

审稿时长

3-8 weeks

期刊介绍： Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.