Kaur Sifat, Verma Reet, Sharma Veerta, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
Metab Brain Dis. 2025 Jun 7;40(5):219. doi: 10.1007/s11011-025-01644-4.
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.
神经退行性疾病的特征是神经元进行性丧失、认知衰退以及由氧化应激和神经炎症驱动的运动功能障碍。NADPH氧化酶（NOX）是中枢神经系统中活性氧（ROS）的主要来源，会导致氧化损伤、线粒体功能障碍和神经炎症反应。NOX酶的过度激活，特别是NOX-1、NOX-2和NOX-4，与神经元损伤和疾病进展有关。NOX抑制剂在临床前模型中显示出了前景，可通过减少ROS生成、调节神经炎症途径以及维持神经元完整性来实现。尽管有这些令人鼓舞的发现，但临床研究仍处于早期阶段，正在进行的研究集中在评估NOX抑制剂在神经退行性疾病中的作用。抑制NOX代表了一种有前景的神经退行性疾病治疗策略。然而，要成功实现临床转化，必须解决诸如实现同工型选择性、提高药物生物利用度以及克服血脑屏障穿透等挑战。本综述提供了关于神经退行性疾病中NOX抑制的治疗观点，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，旨在优化针对NOX的临床应用治疗方法。
