Mgst3, or microsomal glutathione transferase 3, is part of the antioxidant system and is involved in eicosanoid and glutathione metabolism [1,2]. These processes are associated with oxidative stress, apoptosis, and may play a role in the pathophysiology of neurodegenerative and other diseases [1,2]. Genetic models, such as gene knockout mouse models, can be valuable in studying Mgst3's functions.

In neurodegenerative disease-related studies, silencing Mgst3 downregulates the interaction between UBL3 and α-synuclein, which are associated with the pathology of Parkinson's disease [1]. In Alzheimer's disease research, knockdown of Mgst3 in cell lines reduces the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and amyloidogenesis, through a mechanism involving RGS4-mediated AKT signaling pathway [2]. In triple-negative breast cancer, mutant p53 protects cells from ferroptosis via NRF2-dependent regulation of Mgst3, encoding a glutathione-dependent peroxidase that detoxifies lipid peroxides [3].

In conclusion, Mgst3 is essential in antioxidant-related processes and is implicated in multiple disease areas including neurodegenerative diseases like Parkinson's and Alzheimer's, as well as in triple-negative breast cancer. Studies using loss-of-function models have been crucial in revealing its role in these diseases, providing insights into potential disease mechanisms and possible therapeutic targets.

References:

1. Yan, Jing, Zhang, Hengsen, Tomochika, Yuna, Yoshida, Minoru, Setou, Mitsutoshi. 2023. UBL3 Interaction with α-Synuclein Is Downregulated by Silencing MGST3. In Biomedicines, 11, . doi:10.3390/biomedicines11092491. https://pubmed.ncbi.nlm.nih.gov/37760932/

2. Pu, Yalan, Yang, Jie, Pan, Qiuling, Xiao, Fei, Chen, Guojun. 2024. MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway. In The Journal of biological chemistry, 300, 107530. doi:10.1016/j.jbc.2024.107530. https://pubmed.ncbi.nlm.nih.gov/38971310/

3. Dibra, Denada, Xiong, Shunbin, Moyer, Sydney M, Korkut, Anil, Lozano, Guillermina. 2024. Mutant p53 protects triple-negative breast adenocarcinomas from ferroptosis in vivo. In Science advances, 10, eadk1835. doi:10.1126/sciadv.adk1835. https://pubmed.ncbi.nlm.nih.gov/38354236/