OGG1, also known as 8-oxoguanine DNA glycosylase, is a key repair protein for 8-oxoguanine (8-oxoG) in eukaryotic DNA. It functions via the base excision repair (BER) pathway, recognizing and excising 8-oxoG, and then recruiting other proteins to complete the repair. OGG1 is involved in a wide array of physiological processes such as DNA repair, oxidative stress response, inflammation, fibrosis, and autophagy [1].

In terms of disease-related findings, OGG1 plays a significant role in kidney disease progression through DNA repair, inflammation induction, autophagy regulation, and transcriptional regulation [1]. In cancer, targeting OGG1 can arrest cancer cell proliferation by inducing replication stress. OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating it as a potential anti-cancer target [3]. In pulmonary diseases, inhibiting OGG1 with small molecules might be a novel therapeutic strategy as the absence of OGG1 attenuates the binding of transcription factors to cis-elements, modulating pro-inflammatory or pro-fibrotic transcriptional activity [2]. In aging-related neuroinflammation, mitochondrial OGG1 expression can reduce age-associated neuroinflammation by regulating cytosolic mitochondrial DNA. Old male transgenic mice with enhanced mitochondrial-targeted OGG1 (mtOGG1) expression show decreased inflammation response [4]. Also, the OGG1 rs1052133 polymorphism may be associated with the genetic susceptibility to chronic myelogenous leukaemia [5].

In conclusion, OGG1 is crucial for maintaining DNA integrity through its role in the BER pathway and is involved in multiple physiological and pathological processes. Studies using various models, including gene-knockout models in mice for in vivo studies, have revealed its significance in diseases such as kidney diseases, cancer, pulmonary diseases, age-related neuroinflammation, and chronic myelogenous leukaemia. Understanding OGG1's functions provides potential therapeutic targets for these diseases.

References:

1. Zhao, Fan, Zhu, Jiefu, Shi, Lang, Wu, Xiongfei. 2022. OGG1 in the Kidney: Beyond Base Excision Repair. In Oxidative medicine and cellular longevity, 2022, 5774641. doi:10.1155/2022/5774641. https://pubmed.ncbi.nlm.nih.gov/36620083/

2. Pan, Lang, Boldogh, Istvan. 2024. The potential for OGG1 inhibition to be a therapeutic strategy for pulmonary diseases. In Expert opinion on therapeutic targets, 28, 117-130. doi:10.1080/14728222.2024.2317900. https://pubmed.ncbi.nlm.nih.gov/38344773/

3. Visnes, Torkild, Benítez-Buelga, Carlos, Cázares-Körner, Armando, Berglund, Ulrika Warpman, Helleday, Thomas. . Targeting OGG1 arrests cancer cell proliferation by inducing replication stress. In Nucleic acids research, 48, 12234-12251. doi:10.1093/nar/gkaa1048. https://pubmed.ncbi.nlm.nih.gov/33211885/

4. Hussain, Mansoor, Chu, Xixia, Duan Sahbaz, Burcin, Croteau, Deborah L, Bohr, Vilhelm A. 2023. Mitochondrial OGG1 expression reduces age-associated neuroinflammation by regulating cytosolic mitochondrial DNA. In Free radical biology & medicine, 203, 34-44. doi:10.1016/j.freeradbiomed.2023.03.262. https://pubmed.ncbi.nlm.nih.gov/37011700/

5. Hassan, Fathelrahman M. 2019. OGG1 rs1052133 Polymorphism and Genetic Susceptibility to Chronic Myelogenous Leukaemia. In Asian Pacific journal of cancer prevention : APJCP, 20, 925-928. doi:. https://pubmed.ncbi.nlm.nih.gov/30912416/