Notch1 is a crucial gene involved in the Notch signaling pathway, a key mechanism for intercellular coordination. It plays essential roles in cell fate determination during development and is involved in various biological processes such as tissue homeostasis, differentiation, and proliferation [2,3,5].

In leukemia, genetic alterations in NOTCH1 have been identified at a high frequency, suggesting its role in the pathogenesis of the disease, and targeting it may present novel therapeutic options [1]. In ischemic heart disease, aberrant Notch1 signaling exists, and it is involved in endothelial cells, vascular smooth muscle cells, and macrophages, as well as various remodeling stages of the disease, making it a potential target to enhance treatment efficacy [2]. In gastric cancer, the Notch1 signaling pathway promotes growth and metastasis via modulating CDH5, indicating that targeting the Notch1/CDH5 axis could be a potential therapeutic strategy [4].

In conclusion, Notch1 is vital for cell fate determination, tissue homeostasis, and differentiation. Its study through genetic models has revealed its significant roles in diseases like leukemia, ischemic heart disease, and gastric cancer. Understanding Notch1 contributes to a better understanding of disease pathogenesis and may provide new therapeutic strategies for these diseases.

References:

1. Abolhasani, Shiva, Hejazian, Seyyed Sina, Karpisheh, Vahid, Hojjat-Farsangi, Mohammad, Jadidi-Niaragh, Farhad. 2022. The role of SF3B1 and NOTCH1 in the pathogenesis of leukemia. In IUBMB life, 75, 257-278. doi:10.1002/iub.2660. https://pubmed.ncbi.nlm.nih.gov/35848163/

2. Peng, Xiafeng, Wang, Shixin, Chen, Hongwu, Chen, Minglong. 2023. Role of the Notch1 signaling pathway in ischemic heart disease (Review). In International journal of molecular medicine, 51, . doi:10.3892/ijmm.2023.5230. https://pubmed.ncbi.nlm.nih.gov/36799152/

3. Boerkoel, Pierre, Huynh, Stephanie, Yang, Gui Xiang, Terry, Jefferson, Elbert, Adrienne. 2023. NOTCH1 loss of the TAD and PEST domain: An antimorph? In American journal of medical genetics. Part A, 191, 1593-1598. doi:10.1002/ajmg.a.63167. https://pubmed.ncbi.nlm.nih.gov/36866832/

4. Zhou, Lingshan, Yang, Yuan, Ye, Yuwei, Liu, Min, Zhou, Yongning. 2024. Notch1 signaling pathway promotes growth and metastasis of gastric cancer via modulating CDH5. In Aging, 16, 11893-11903. doi:10.18632/aging.206061. https://pubmed.ncbi.nlm.nih.gov/39172098/

5. Padovano, Costanzo, Bianco, Salvatore Daniele, Sansico, Francesca, Mazza, Tommaso, Giambra, Vincenzo. 2023. The Notch1 signaling pathway directly modulates the human RANKL-induced osteoclastogenesis. In Scientific reports, 13, 21199. doi:10.1038/s41598-023-48615-2. https://pubmed.ncbi.nlm.nih.gov/38040752/