Targeting NOX inhibitors in neurodegeneration: a therapeutic perspective.

IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Sifat Kaur, Reet Verma, Veerta Sharma, Thakur Gurjeet Singh
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引用次数: 0

Abstract

Neurodegenerative diseases are characterized by progressive neuronal loss, cognitive decline, and motor dysfunction driven by oxidative stress and neuroinflammation. NADPH oxidases (NOX) are a major source of reactive oxygen species (ROS) in the central nervous system, contributing to oxidative damage, mitochondrial dysfunction, and neuroinflammatory responses. Overactivation of NOX enzymes, particularly NOX-1, NOX-2, and NOX-4, has been implicated in neuronal injury and disease progression. NOX inhibitors have shown promise in pre-clinical models by reducing ROS production, modulating neuroinflammatory pathways, and preserving neuronal integrity. Despite these encouraging findings, clinical research remains in early stages, with ongoing studies focused on evaluating NOX inhibitors in neurodegeneration. NOX inhibition represents a promising therapeutic strategy for neurodegeneration. However, challenges such as achieving isoform selectivity, improving drug bioavailability, and overcoming blood-brain barrier penetration must be addressed for successful clinical translation. This review provides a therapeutic perspective on NOX inhibition in neurodegenerative diseases, discussing the current state of pre-clinical and clinical research, highlighting key challenges, and proposing directions for future research aimed at optimizing NOX-targeted therapies for clinical application.

靶向氮氧化物抑制剂在神经退行性变:治疗的角度。
神经退行性疾病的特征是由氧化应激和神经炎症驱动的进行性神经元丧失、认知能力下降和运动功能障碍。NADPH氧化酶(NOX)是中枢神经系统活性氧(ROS)的主要来源,有助于氧化损伤、线粒体功能障碍和神经炎症反应。NOX酶,特别是NOX-1、NOX-2和NOX-4的过度激活与神经元损伤和疾病进展有关。NOX抑制剂通过减少ROS的产生、调节神经炎症通路和保持神经元完整性,在临床前模型中显示出前景。尽管有这些令人鼓舞的发现,临床研究仍处于早期阶段,正在进行的研究主要集中在评估氮氧化物抑制剂在神经变性中的作用。抑制氮氧化物是一种很有前途的神经退行性疾病治疗策略。然而,实现异构体选择性、提高药物生物利用度和克服血脑屏障渗透等挑战必须得到解决,才能成功地进行临床翻译。本文综述了神经退行性疾病中NOX抑制的治疗角度,讨论了临床前和临床研究的现状,强调了关键挑战,并提出了未来研究的方向,旨在优化NOX靶向治疗以用于临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Metabolic brain disease
Metabolic brain disease 医学-内分泌学与代谢
CiteScore
5.90
自引率
5.60%
发文量
248
审稿时长
6-12 weeks
期刊介绍: Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.
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