Nme8, a member of the NME family, contains thioredoxin and NDPK domains. Some NME family proteins are involved in DNA proofreading and repair due to their 3'-5' exonuclease activity, suggesting a potential role for Nme8 in similar processes [5]. It has been associated with multiple biological functions and disease conditions, highlighting its overall biological importance. Genetic models, such as mouse models, can be valuable for studying Nme8's functions.

In mice, deletion of exons 6-7 of Nme8 based on human mutation sites led to impaired transcript splicing. Nme8 was not essential for spermatogenesis, possibly due to functional compensation by its paralog, Nme5. However, under cisplatin (CP) treatment, Nme8 deficiency further impaired antioxidant capacity, induced lipid peroxidation, increased ROS level, failed to activate autophagy, and resulted in aggravated DNA damage in testes and sperm. This halted the proliferation and differentiation of spermatogonia, the meiosis of spermatocyte, and impaired sperm motility, indicating that NME8 protects against CP-induced testis and sperm damage [1].

In conclusion, Nme8 plays a crucial role in protecting against cisplatin-induced male reproductive toxicity in mice. Mouse models have been instrumental in revealing this role, providing new insights into the physiological functions of the Nme family and potential targets for preserving fertility in young male cancer patients. Additionally, Nme8 has been associated with Alzheimer's disease and idiopathic normal pressure hydrocephalus (iNPH), though the exact nature of its role in these conditions requires further investigation [1,2,3,4,6,7,8].

References:

1. Zhu, Haixia, Wang, Hongxiang, Wang, Dan, Liu, Min, Gao, Jiangang. 2024. Nme8 is essential for protection against chemotherapy drug cisplatin-induced male reproductive toxicity in mice. In Cell death & disease, 15, 730. doi:10.1038/s41419-024-07118-2. https://pubmed.ncbi.nlm.nih.gov/39368984/

2. Karch, Celeste M, Goate, Alison M. 2014. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. In Biological psychiatry, 77, 43-51. doi:10.1016/j.biopsych.2014.05.006. https://pubmed.ncbi.nlm.nih.gov/24951455/

3. Kim, Jong Hun. 2019. Genetics of Alzheimer's Disease. In Dementia and neurocognitive disorders, 17, 131-136. doi:10.12779/dnd.2018.17.4.131. https://pubmed.ncbi.nlm.nih.gov/30906402/

4. Liu, Shu-Lei, Wang, Xue-Chun, Tan, Meng-Shan, Yu, Jin-Tai, Tan, Lan. . NME8 rs2718058 polymorphism with Alzheimer's disease risk: a replication and meta-analysis. In Oncotarget, 7, 36014-36020. doi:10.18632/oncotarget.9086. https://pubmed.ncbi.nlm.nih.gov/27144521/

5. Puts, Gemma S, Leonard, M Kathryn, Pamidimukkala, Nidhi V, Snyder, Devin E, Kaetzel, David M. 2017. Nuclear functions of NME proteins. In Laboratory investigation; a journal of technical methods and pathology, 98, 211-218. doi:10.1038/labinvest.2017.109. https://pubmed.ncbi.nlm.nih.gov/29058704/

6. Leinonen, Ville, Kuulasmaa, Teemu, Hiltunen, Mikko. 2021. iNPH-the mystery resolving. In EMBO molecular medicine, 13, e13720. doi:10.15252/emmm.202013720. https://pubmed.ncbi.nlm.nih.gov/33555136/

7. Liu, Ying, Yu, Jin-Tai, Wang, Hui-Fu, Zhang, Dao-Qiang, Tan, Lan. 2014. Association between NME8 locus polymorphism and cognitive decline, cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease. In PloS one, 9, e114777. doi:10.1371/journal.pone.0114777. https://pubmed.ncbi.nlm.nih.gov/25486118/

8. Chouraki, Vincent, Seshadri, Sudha. . Genetics of Alzheimer's disease. In Advances in genetics, 87, 245-94. doi:10.1016/B978-0-12-800149-3.00005-6. https://pubmed.ncbi.nlm.nih.gov/25311924/