Ctsb, also known as Cathepsin B, is a cysteine protease that has a significant role in various biological processes. It is associated with lysosomal-related cell structures and pathways and is involved in cell death mechanisms such as apoptosis, pyroptosis, and necroptosis [1,2,7]. It is also related to immune responses, inflammation, and metabolism [5,6]. Genetic models, especially knockout (KO) mouse models, can be valuable for studying its function.

In sepsis-induced acute kidney injury (S-AKI), inhibition of Ctsb by CA074 could reverse lipopolysaccharide (LPS)-induced apoptosis of HK-2 cells, suggesting Ctsb promotes S-AKI through activating mitochondrial apoptosis pathway [1]. In high-fat-diet-induced hepatic pyroptosis, apigenin alleviated pyroptosis by reducing Ctsb release caused by lysosomal membrane permeabilization (LMP) through the mitophagy-ROS-Ctsb-NLRP3 pathway [2]. In breast cancer bone metastasis, CST6 protein inhibits osteoclastogenesis and bone metastasis by suppressing Ctsb activity [3]. In HL-60 cells (related to adult leukemia), knockdown of Ctsb inhibited cell proliferation and tumorigenesis, potentially through inactivation of the AKT signaling pathway [4].

In conclusion, Ctsb is involved in multiple biological processes and diseases. Studies using KO or functional inhibition models have revealed its role in cell death, inflammation, and tumor-related processes. Understanding Ctsb function provides potential therapeutic strategies for diseases like S-AKI, liver injury, breast cancer bone metastasis, and leukemia [1-4].

References:

1. Wang, Yuting, Xi, Wenjie, Zhang, Xinyi, Zheng, Xiaoming, Chi, Xinjin. 2023. CTSB promotes sepsis-induced acute kidney injury through activating mitochondrial apoptosis pathway. In Frontiers in immunology, 13, 1053754. doi:10.3389/fimmu.2022.1053754. https://pubmed.ncbi.nlm.nih.gov/36713420/

2. Meng, Zhuoqun, Gao, Min, Wang, Chunyun, Zhang, DuoDuo, Lu, Jing. 2023. Apigenin Alleviated High-Fat-Diet-Induced Hepatic Pyroptosis by Mitophagy-ROS-CTSB-NLRP3 Pathway in Mice and AML12 Cells. In Journal of agricultural and food chemistry, 71, 7032-7045. doi:10.1021/acs.jafc.2c07581. https://pubmed.ncbi.nlm.nih.gov/37141464/

3. Li, Xiaoxun, Liang, Yajun, Lian, Cheng, Liu, Tong, Hu, Guohong. 2021. CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis. In Theranostics, 11, 9821-9832. doi:10.7150/thno.62187. https://pubmed.ncbi.nlm.nih.gov/34815788/

4. Peng, Sida, Yang, Qingqing, Li, Huan, Hu, Pan, Zhang, Nana. 2021. CTSB Knockdown Inhibits Proliferation and Tumorigenesis in HL-60 Cells. In International journal of medical sciences, 18, 1484-1491. doi:10.7150/ijms.54206. https://pubmed.ncbi.nlm.nih.gov/33628106/

5. Ma, Kaiming, Chen, Xin, Liu, Weihai, Yang, Chenlong, Yang, Jun. 2022. CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas. In Scientific reports, 12, 4295. doi:10.1038/s41598-022-08346-2. https://pubmed.ncbi.nlm.nih.gov/35277559/

6. Gaitán, Julian M, Moon, Hyo Youl, Stremlau, Matthew, Okonkwo, Ozioma C, van Praag, Henriette. 2021. Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease. In Frontiers in endocrinology, 12, 660181. doi:10.3389/fendo.2021.660181. https://pubmed.ncbi.nlm.nih.gov/34093436/

7. Liu, Shuzhen, Perez, Preston, Sun, Xue, Mammadova, Jamila, Wang, Zhigao. 2023. MLKL polymerization-induced lysosomal membrane permeabilization promotes necroptosis. In Cell death and differentiation, 31, 40-52. doi:10.1038/s41418-023-01237-7. https://pubmed.ncbi.nlm.nih.gov/37996483/