SELENOW, also known as selenoprotein W and SEPW1, is a selenocysteine-containing protein. It is involved in multiple biological functions, especially those related to redox homeostasis as it belongs to the thioredoxin-like family of selenoproteins [4,6]. Its functions may be associated with various pathways in different tissues and cell types, highlighting its overall biological importance. Genetic models, such as KO mouse models, have been crucial in studying its functions.

In sarcopenia, SELENOW KO in mouse models aggravated muscle mass loss. It suppressed the RAC1-mTOR cascade through interaction with RAC1, leading to an imbalance in protein synthesis and degradation. Conversely, overexpression of SELENOW alleviated muscle and myotube atrophy induced by dexamethasone, indicating its role in regulating age-related sarcopenia [1]. In an Alzheimer's disease mouse model, SELENOW deficiency led to synaptic defects, tau dysregulation, and memory deficits. Overexpression in triple transgenic AD mice ameliorated memory impairment and tau-related pathologies, showing its role in regulating tau homeostasis [2]. In non-alcoholic fatty liver disease, loss of SelW (SELENOW) alleviated hepatic steatosis induced by a high-fat diet, accompanied by the regulation of metabolic and inflammatory pathways. SelW also interacted with PKM2, modulating its translocation into the nucleus, which further affected mitochondrial apoptosis, ROS production, and macrophage phenotype, thus exacerbating NAFLD progression [3]. In osteoclast differentiation, SELENOW-deficient mice exhibited a high bone mass phenotype, while SELENOW-overexpressing mice had osteoporosis. SELENOW overexpression enhanced osteoclastogenesis in vitro, indicating its role in physiological bone remodeling [5].

In conclusion, model-based research, especially through KO mouse models, has revealed that SELENOW plays essential roles in multiple biological processes and disease conditions. These include muscle mass regulation in sarcopenia, tau homeostasis in Alzheimer's disease, hepatic steatosis in non-alcoholic fatty liver disease, and bone remodeling. Understanding SELENOW's functions can potentially provide new insights for the prevention and treatment of these diseases.

References:

1. Yang, Jia-Cheng, Liu, Meng, Huang, Rong-Hui, Lei, Xin Gen, Sun, Lv-Hui. 2024. Loss of SELENOW aggravates muscle loss with regulation of protein synthesis and the ubiquitin-proteasome system. In Science advances, 10, eadj4122. doi:10.1126/sciadv.adj4122. https://pubmed.ncbi.nlm.nih.gov/39303039/

2. Ren, Bingyu, Situ, Jiaxin, Huang, Xuelian, Ni, Jiazuan, Liu, Qiong. 2024. Selenoprotein W modulates tau homeostasis in an Alzheimer's disease mouse model. In Communications biology, 7, 872. doi:10.1038/s42003-024-06572-0. https://pubmed.ncbi.nlm.nih.gov/39020075/

3. Miao, Zhiruo, Wang, Wei, Miao, Zhiying, Cao, Qiyuan, Xu, Shiwen. 2024. Role of Selenoprotein W in participating in the progression of non-alcoholic fatty liver disease. In Redox biology, 71, 103114. doi:10.1016/j.redox.2024.103114. https://pubmed.ncbi.nlm.nih.gov/38460355/

4. Gladyshev, Vadim N, Arnér, Elias S, Berry, Marla J, Whanger, Philip D, Zhang, Yan. 2016. Selenoprotein Gene Nomenclature. In The Journal of biological chemistry, 291, 24036-24040. doi:. https://pubmed.ncbi.nlm.nih.gov/27645994/

5. Kim, Hyunsoo, Lee, Kyunghee, Kim, Jin Man, Choi, Yongwon, Jeong, Daewon. 2021. Selenoprotein W ensures physiological bone remodeling by preventing hyperactivity of osteoclasts. In Nature communications, 12, 2258. doi:10.1038/s41467-021-22565-7. https://pubmed.ncbi.nlm.nih.gov/33859201/

6. Zhang, Li, Zhu, Jian-Hong, Zhang, Xiong, Cheng, Wen-Hsing. 2018. The Thioredoxin-Like Family of Selenoproteins: Implications in Aging and Age-Related Degeneration. In Biological trace element research, 188, 189-195. doi:10.1007/s12011-018-1521-9. https://pubmed.ncbi.nlm.nih.gov/30229511/