Ndrg4, short for N-myc downstream-regulated gene 4, is involved in multiple biological processes and disease-related pathways. It has been associated with apoptosis-related pathways and tumor-suppressor functions. Its study in genetic models can help uncover its precise roles in normal and disease states [1,2,3,4].

In various disease models, Ndrg4 shows significant effects. In cerebral ischemia/reperfusion injury models, Ndrg4 restoration via adenovirus reduces infarct sizes and neuronal apoptosis, regulating the expression of apoptosis-related proteins like Bcl-2, Bax, caspase-3, and c-Fos, and increasing BDNF expression [2]. In a cerebral ischemia injury model, Ndrg4 overexpression decreases infarct size and mitigates neurological deficits by inhibiting p53-mediated mitochondrial apoptosis signaling [3]. In colorectal cancer (CRC) cells, Ndrg4 inhibits cell proliferation, activates apoptosis, and sensitizes CRC cells to 5-FU by upregulating DDIT3 expression, while also inhibiting the PI3K/AKT and ERK signaling pathways [1]. In gastric cancer, Ndrg4 protein and mRNA expression is decreased compared to adjacent normal specimens, and its overexpression suppresses cell proliferation in vitro [4].

In conclusion, Ndrg4 plays crucial roles in preventing cell apoptosis in conditions such as cerebral ischemia-related injuries and acts as a potential tumor suppressor in cancers like CRC and gastric cancer. The study of Ndrg4 in these models helps understand its biological functions in disease development, potentially providing new therapeutic targets for these diseases.

References:

1. Li, Ruikai, He, Chenxiang, Shen, Liangliang, Zhang, Jian, Zheng, Jianyong. 2021. NDRG4 sensitizes CRC cells to 5-FU by upregulating DDIT3 expression. In Oncology letters, 22, 782. doi:10.3892/ol.2021.13043. https://pubmed.ncbi.nlm.nih.gov/34594423/

2. Wen, Lan, Liu, Lei, Tong, Linyan, Zhang, Qinbin, Li, Changqing. 2019. NDRG4 prevents cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis. In Genes & diseases, 6, 448-454. doi:10.1016/j.gendis.2019.01.001. https://pubmed.ncbi.nlm.nih.gov/31832525/

3. Wen, Lan, Liu, Lei, Li, Jinfang, Zhang, Qinbin, Li, Changqing. 2018. NDRG4 protects against cerebral ischemia injury by inhibiting p53-mediated apoptosis. In Brain research bulletin, 146, 104-111. doi:10.1016/j.brainresbull.2018.12.010. https://pubmed.ncbi.nlm.nih.gov/30593880/

4. Zhang, Zixi, She, Junjun, Yang, Jingyi, He, Shuixiang, Chu, Dake. 2018. NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome. In Molecular carcinogenesis, 57, 762-771. doi:10.1002/mc.22798. https://pubmed.ncbi.nlm.nih.gov/29500881/