期刊文献

Signaling Pathways in Oxidative Stress-Induced Neurodegenerative Diseases: A Review of Phytochemical Therapeutic Interventions 收藏

氧化应激引起的神经退行性疾病中的信号通路：植物化学治疗干预的综述

原文求助发布源

作者

Zahra Sebghatollahi [1];Ruchika Yogesh (https://orcid.org/0000-0001-8017-0840) [2];Neelima Mahato (https://orcid.org/0000-0001-8293-0997) [3];Vijay Kumar (https://orcid.org/0000-0002-8035-9181) [4];Yugal Kishore Mohanta (https://orcid.org/0000-0002-6547-7227) [5];Kwang-Hyun Baek (https://orcid.org/0000-0002-6719-9187) [6];Awdhesh Kumar Mishra (https://orcid.org/0000-0002-3312-3264) [7];

作者单位

[1]Department of Plant Breeding and Biotechnology, Faculty of Agricultural Sciences and Food Industries, Science and Research Branch, Islamic Azad University, Tehran 1477893855, Iran; [2]MaTestLab Inc., 2093 Philadelphia Pike, Claymont, DE 19703, USA; [3]School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Gyeongsangbuk-do, Republic of Korea; [4]Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; [5]Nano-Biotechnology and Translational Knowledge Laboratory, Department of Applied Biology, School of Biological Sciences, University of Science and Technology Meghalaya, Techno City, 9th Mile, Baridua 793101, Meghalaya, India; [6]Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Gyeongsangbuk-do, Republic of Korea; [7]Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Gyeongsangbuk-do, Republic of Korea;

发布日期

2025-4-12

页码

457

DOI

10.3390/antiox14040457

来源信息

Antioxidants ISSN：2076-3921, 2025年, 14卷, 4期, 457页

摘要

Oxidative stress, a pivotal driver of neurodegenerative diseases, results from an imbalance between the generation of reactive oxygen species (ROS) and cellular antioxidant defenses. This review provides a comprehensive analysis of key oxidative stress sources, focusing on NADPH oxidase (NOX) hyperactivity and mitochondrial Uncoupling Protein (UCP) downregulation. Critically, we examine the therapeutic potential of phytochemicals in mitigating NOX-mediated ROS generation through direct enzyme inhibition, including impacts on NOX subunit assembly and gene expression. Furthermore, we explore the ability of phytochemicals to bolster cellular antioxidant defenses by activating the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway, elucidating the upregulation of antioxidant genes, such as GPx, SOD, CAT, and HO-1. This review expands beyond confined overviews; emphasizes specific molecular interactions between phytochemicals and target proteins, including NOX isoforms; and provides an in-depth analysis of the specific antioxidant genes upregulated via Nrf2. This approach aims to pave the way for targeted and translatable therapeutic strategies in neurodegenerative diseases. Ultimately, this review illuminates the intricate molecular dynamics of oxidative stress in neurodegenerative diseases; underscores the potential of phytochemicals to restore redox homeostasis and reverse pathological conditions through precise modulation of key signaling pathways.

摘要译文

氧化应激是神经退行性疾病的关键驱动因素，是由于活性氧（ROS）和细胞抗氧化剂防御剂的产生之间的不平衡引起的。这篇综述提供了关键氧化应激源的全面分析，重点是NADPH氧化酶（NOX）多动和线粒体解偶联蛋白（UCP）下调。至关重要的是，我们检查了植物化学物质通过直接酶抑制作用减轻NOX介导的ROS产生的治疗潜力，包括对NOX亚基组装和基因表达的影响。此外，我们通过激活类似kelch的ECHECE相关蛋白1（KEAP1）/核因子2相关因子2（NRF2）/抗氧化反应元件（是抗氧化元素（是）信号传播的信号途径，Elcoped cate nocedant catex and cate tosexeant catex tosevant catex catex cate，我们探索了植物化学物质通过激活类似kelch的kelch kelch样蛋白1（Keap1）/核因子2相关因子2（NRF2）/核因子2相关因子2（NRF2）的能力来增强细胞抗氧化剂的防御能力。和HO-1。这篇评论扩展了超越限制的概述；强调植物化学物质和靶蛋白（包括NOX同工型）之间的特定分子相互作用；并提供了对通过NRF2上调的特定抗氧化基因的深入分析。这种方法旨在为神经退行性疾病的靶向和可翻译治疗策略铺平道路。最终，这篇评论阐明了神经退行性疾病中氧化应激的复杂分子动力学。通过精确调节关键信号通路，强调了植物化学物质恢复氧化还原稳态和逆向病理条件的潜力。