Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Zhuhai UM Science and Technology Research Institute, Zhuhai, China.
Med Res Rev. 2024 Nov;44(6):2825-2848. doi: 10.1002/med.22068. Epub 2024 Aug 9.
Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms. We also highlight the potential of OGG1 inhibitors and activators as potent therapeutic agents for the aforementioned life-limiting diseases. We conclude that OGG1 serves as a multifunctional hub; the inhibition of OGG1 may provide a novel approach for preventing and treating inflammation and cancer, and the activation of OGG1 could be a strategy for preventing age-related disorders. Furthermore, we provide an extensive overview of successful applications of OGG1 regulation in treating inflammatory, cancerous, and aging-related diseases. Finally, we discuss the current challenges and future directions of OGG1 as an emerging multifunctional therapeutic marker for the aforementioned challenging diseases. The aim of this review is to provide a robust reference for scientific researchers and clinical drug developers in the development of novel clinical targeted drugs for life-limiting diseases, especially for incurable inflammation, malignant tumors, and age-related disorders.
氧化 DNA 损伤相关疾病,如无法治愈的炎症、恶性肿瘤和与年龄相关的疾病,由于其复杂的分子机制和有效治疗靶点识别的局限性,在现代医学中构成重大挑战。最近,8-氧鸟嘌呤 DNA 糖基化酶 1(OGG1)已成为治疗这些挑战性疾病的有前途的多功能治疗靶点。在这篇综述中,我们系统地总结了 OGG1 的多种功能和机制,包括促炎、致瘤和衰老调节机制。我们还强调了 OGG1 抑制剂和激活剂作为治疗上述危及生命疾病的潜在有效治疗药物的潜力。我们得出结论,OGG1 是一种多功能枢纽;抑制 OGG1 可能为预防和治疗炎症和癌症提供一种新方法,而激活 OGG1 可能是预防与年龄相关疾病的一种策略。此外,我们广泛概述了 OGG1 调节在治疗炎症、癌症和与衰老相关疾病方面的成功应用。最后,我们讨论了 OGG1 作为新兴的多功能治疗标志物在治疗上述挑战性疾病方面的当前挑战和未来方向。本综述的目的是为科学研究人员和临床药物开发者提供强有力的参考,以开发用于治疗危及生命疾病的新型临床靶向药物,特别是用于治疗无法治愈的炎症、恶性肿瘤和与年龄相关的疾病。