NQO1, also known as NAD(P)H: quinone oxidoreductase 1, is an antioxidant enzyme that uses NADH or NADPH as substrates to reduce quinones to hydroquinones, protecting cells from oxidative stress. It is involved in multiple functions such as superoxide reductase activity, NAD+ generation, and protein stabilization. It is also associated with various pathways including those related to redox control, glucose and insulin metabolism, and has a significant role in maintaining cellular homeostasis [1,7].

In diabetic nephropathy, NQO1 alleviates renal fibrosis by inhibiting the TLR4/NF-κB and TGF-β/Smad signaling pathways. Overexpression of NQO1 in the kidneys of type 2 diabetes model db/db mice suppressed pro-inflammatory cytokine secretion, extracellular matrix accumulation, and epithelial-mesenchymal transition [2]. In drug-resistant non-small cell lung cancer, the NQO1 substrate 2-methoxy-6-acetyl-7-methyljuglone (MAM) induced ferroptosis by targeting NQO1, indicating its potential in fighting drug-resistant cancer [3]. In the central nervous system, NQO1 is crucial for neuronal function, and its dysregulation is linked to multiple neurological disorders including Parkinson's disease, Alzheimer's disease, and brain malignancies [4]. In ovarian cancer, NQO1's antioxidant function may impact cancer onset and progression [5]. Its high expression in many solid tumors has led to the development of NQO1-responsive prodrugs and nanocarriers for cancer treatment [6].

In conclusion, NQO1 is an essential enzyme with diverse functions in maintaining cellular redox balance and normal physiological processes. Studies, including those using relevant animal models, have revealed its significance in various disease areas such as diabetes-related kidney diseases, cancer, and neurological disorders. Understanding NQO1 can potentially provide new therapeutic strategies for these diseases.

References:

1. Ross, David, Siegel, David. 2021. The diverse functionality of NQO1 and its roles in redox control. In Redox biology, 41, 101950. doi:10.1016/j.redox.2021.101950. https://pubmed.ncbi.nlm.nih.gov/33774477/

2. Qiu, Duojun, Song, Shan, Chen, Ning, Duan, Huijun, Shi, Yonghong. 2023. NQO1 alleviates renal fibrosis by inhibiting the TLR4/NF-κB and TGF-β/Smad signaling pathways in diabetic nephropathy. In Cellular signalling, 108, 110712. doi:10.1016/j.cellsig.2023.110712. https://pubmed.ncbi.nlm.nih.gov/37196773/

3. Yu, Jie, Zhong, Bingling, Zhao, Lin, Ge, Wei, Chen, Xiuping. 2023. Fighting drug-resistant lung cancer by induction of NAD(P)H:quinone oxidoreductase 1 (NQO1)-mediated ferroptosis. In Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 70, 100977. doi:10.1016/j.drup.2023.100977. https://pubmed.ncbi.nlm.nih.gov/37321064/

4. Yuhan, Li, Khaleghi Ghadiri, Maryam, Gorji, Ali. 2024. Impact of NQO1 dysregulation in CNS disorders. In Journal of translational medicine, 22, 4. doi:10.1186/s12967-023-04802-3. https://pubmed.ncbi.nlm.nih.gov/38167027/

5. Tossetta, Giovanni, Fantone, Sonia, Goteri, Gaia, Ciavattini, Andrea, Marzioni, Daniela. 2023. The Role of NQO1 in Ovarian Cancer. In International journal of molecular sciences, 24, . doi:10.3390/ijms24097839. https://pubmed.ncbi.nlm.nih.gov/37175546/

6. Yang, Xiaojuan, Duan, Jiaxue, Wu, Liqiang. 2022. Research advances in NQO1-responsive prodrugs and nanocarriers for cancer treatment. In Future medicinal chemistry, 14, 363-383. doi:10.4155/fmc-2021-0289. https://pubmed.ncbi.nlm.nih.gov/35102756/

7. Preethi, S, Arthiga, K, Patil, Amit B, Spandana, Asha, Jain, Vikas. 2022. Review on NAD(P)H dehydrogenase quinone 1 (NQO1) pathway. In Molecular biology reports, 49, 8907-8924. doi:10.1007/s11033-022-07369-2. https://pubmed.ncbi.nlm.nih.gov/35347544/