Casp1, also known as Caspase-1, is a gene encoding proteins related to cell death. It is a key component of the inflammasome, which plays a crucial role in the innate immune response by processing and activating pro-inflammatory cytokines like interleukin-1β (IL-1β) and IL-18 [6]. It is involved in pathways such as the regulation of pyroptosis, a type of programmed cell death, and has significance in various biological processes including inflammation and immunity [1,3]. Gene knockout (KO) and conditional knockout (CKO) mouse models are valuable for studying Casp1 function.

In pancreatic cancer, knockdown of Casp1 inhibited cell viability and migration, and enhanced gemcitabine-induced cell death, suggesting it as a potential target for combination therapy [1]. In acute myeloid leukemia (AML), high Casp1 expression was associated with poor prognosis, and its inhibition impaired AML cell proliferation [2]. In acute promyelocytic leukemia (APL), all-trans-retinoic acid (ATRA) induced and activated Casp1, triggering pyroptosis and differentiation of APL cells [3]. In Alzheimer's disease, strongly enhanced active caspase-1 expression was observed, and Nlrp3(-/-) or Casp1(-/-) mice carrying Alzheimer's-associated mutations were protected from memory loss and other sequelae, highlighting the role of the NLRP3/Casp1 axis in the disease [4]. In breast cancer, high Casp1 expression was associated with better survival, and it may affect the cell cycle, immune environment, and inflammation [7]. Also, in coronary stenting, certain Casp1 gene polymorphisms and gene-gene interactions were associated with an increased restenosis risk [5].

In conclusion, Casp1 is essential in regulating cell death, inflammation, and immunity. Studies using KO or CKO mouse models have revealed its roles in multiple disease areas such as cancer, neurodegenerative diseases, and cardiovascular diseases. Understanding Casp1 function provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Wang, Xianfeng, Chen, Zheng, Nie, Dingrui, Li, Yangqiu, Zeng, Chengwu. 2023. CASP1 is a target for combination therapy in pancreatic cancer. In European journal of pharmacology, 961, 176175. doi:10.1016/j.ejphar.2023.176175. https://pubmed.ncbi.nlm.nih.gov/37949157/

2. Liu, Jing, Zhao, Minyi, Feng, Xiaohui, Zeng, Yunxin, Lin, Dongjun. 2021. Expression and prognosis analyses of CASP1 in acute myeloid leukemia. In Aging, 13, 14088-14108. doi:10.18632/aging.203028. https://pubmed.ncbi.nlm.nih.gov/33999861/

3. Yu, Xibao, Liu, Xin, Liu, Xuan, Li, Yangqiu, Zeng, Chengwu. 2023. Overexpression of CASP1 triggers acute promyelocytic leukemia cell pyroptosis and differentiation. In European journal of pharmacology, 945, 175614. doi:10.1016/j.ejphar.2023.175614. https://pubmed.ncbi.nlm.nih.gov/36822457/

4. Heneka, Michael T, Kummer, Markus P, Stutz, Andrea, Latz, Eicke, Golenbock, Douglas T. 2012. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. In Nature, 493, 674-8. doi:10.1038/nature11729. https://pubmed.ncbi.nlm.nih.gov/23254930/

5. Vargas-Alarcón, Gilberto, Ramírez-Bello, Julian, Peña-Duque, Marco Antonio, Delgadillo-Rodríguez, Hilda, Fragoso, José Manuel. 2022. CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene-Gene Interactions Are Associated with Restenosis after Coronary Stenting. In Biomolecules, 12, . doi:10.3390/biom12060765. https://pubmed.ncbi.nlm.nih.gov/35740890/

6. Kayagaki, Nobuhiko, Warming, Søren, Lamkanfi, Mohamed, Roose-Girma, Merone, Dixit, Vishva M. 2011. Non-canonical inflammasome activation targets caspase-11. In Nature, 479, 117-21. doi:10.1038/nature10558. https://pubmed.ncbi.nlm.nih.gov/22002608/

7. Peng, Juan, Wei, Qiang, Zhou, Shibo, Gu, Zhutong, Lv, Kangtai. 2023. Effect of caspase-1 (CASP1) combined with multimodal ultrasound features on the prognosis of breast cancer patients. In Translational cancer research, 12, 2138-2154. doi:10.21037/tcr-23-1135. https://pubmed.ncbi.nlm.nih.gov/37701103/