Cend1, also known as cell-cycle exit and neuronal differentiation 1, is a neuronal lineage-specific modulator. It plays a crucial role in coordinating cell cycle exit and differentiation of neuronal precursors. It acts via the p53-dependent/Cyclin D1/pRb signaling pathway as well as a p53-independent route involving RanBPM and Dyrk1B. Cend1 is essential for the formation of a structurally and functionally normal brain and may have implications in CNS repair [2].

In Alzheimer's disease (AD), Cend1 deficiency in 5xFAD mice leads to mitochondrial dysfunction and cognitive impairment. Depletion of Cend1 increases mitochondrial fission mediated by Drp1 upregulation, resulting in abnormal mitochondrial functions. Overexpression of Cend1 in the hippocampus of 5xFAD mice rescues cognitive deficits. Also, CDK5/p25 interacts with and phosphorylates Cend1, promoting its degradation [1]. In glioma, down-regulation of Cend1 expression contributes to tumor progression and temozolomide resistance. Cend1 inhibits glioma cell proliferation, migration, invasion, and resistance to temozolomide by inhibiting the NF-κB pathway [3].

In summary, Cend1 is vital for normal brain development and function, playing a key role in processes like cell cycle regulation and neuronal differentiation. Studies using gene-knockout models, such as in AD and glioma, have revealed its significance in disease-related mechanisms. Understanding Cend1's functions provides potential insights into treating neurodegenerative diseases and glioma [1,2,3].

References:

1. Xie, Wenting, Guo, Dong, Li, Jieyin, Gao, Weiwei, Zhang, Jie. 2022. CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer's disease. In Cell death and differentiation, 29, 2417-2428. doi:10.1038/s41418-022-01027-7. https://pubmed.ncbi.nlm.nih.gov/35732922/

2. Gaitanou, Maria, Segklia, Katerina, Matsas, Rebecca. 2019. Cend1, a Story with Many Tales: From Regulation of Cell Cycle Progression/Exit of Neural Stem Cells to Brain Structure and Function. In Stem cells international, 2019, 2054783. doi:10.1155/2019/2054783. https://pubmed.ncbi.nlm.nih.gov/31191667/

3. Houjun, Zhou, Peng, Bai. 2023. Down-Regulation of CEND1 Expression Contributes to The Progression and Temozolomide Resistance of Glioma. In Cell journal, 25, 264-272. doi:10.22074/cellj.2022.557561.1074. https://pubmed.ncbi.nlm.nih.gov/37210647/