Ctsz, also known as Cathepsin Z, is a lysosomal cysteine protease of the papain superfamily. It participates in host immune defense via processes like phagocytosis, signal transduction, and the proliferation and migration of immune cells such as monocytes, macrophages, and dendritic cells [4]. It may also be involved in autophagy-related lysosomal function [1].

In Alzheimer's disease (AD) mouse models, long-term treatment with urolithin A (UA) restored lysosomal functions in part by regulating Ctsz protein, improving learning, memory, and olfactory function, reducing amyloid beta and tau pathologies, and enhancing long-term potentiation [1]. In cancer research, in multiple myeloma cells, PDCD4 promotes apoptosis by binding to the 5' UTR of Ctsz and inhibiting its translation [3]. In non-small cell lung cancer cells, deguelin inhibits metastasis by suppressing Ctsz expression and interrupting its interaction with integrin β3, as well as inhibiting the activation of Ctsz downstream FAK/Src/Paxillin signaling [5]. In addition, in a Chinese population, altered Ctsz methylation levels in peripheral blood may be associated with breast cancer, especially in young women, and could serve as a potential biomarker for early-stage BC [2].

In conclusion, Ctsz plays crucial roles in immune defense, autophagy-related lysosomal function, and is involved in the pathogenesis of diseases such as Alzheimer's disease and various cancers. Research using mouse models in Alzheimer's disease and in vitro cell-based functional studies in cancer have significantly advanced our understanding of Ctsz's functions in these disease conditions, providing potential targets for treatment.

References:

1. Hou, Yujun, Chu, Xixia, Park, Jae-Hyeon, Croteau, Deborah L, Bohr, Vilhelm A. 2024. Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions. In Alzheimer's & dementia : the journal of the Alzheimer's Association, 20, 4212-4233. doi:10.1002/alz.13847. https://pubmed.ncbi.nlm.nih.gov/38753870/

2. Li, Jinyu, Zhou, Xiajie, Li, Lixi, Ma, Fei, Dai, Liping. 2023. The association between CTSZ methylation in peripheral blood and breast cancer in Chinese women. In Frontiers in oncology, 13, 1148635. doi:10.3389/fonc.2023.1148635. https://pubmed.ncbi.nlm.nih.gov/37274256/

3. Liu, Liyuan, Feng, Xiumei, Fan, Chenliu, Jiang, Yang, Zheng, Chengyun. . PDCD4 interacting with PIK3CB and CTSZ promotes the apoptosis of multiple myeloma cells. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e70024. doi:10.1096/fj.202400687R. https://pubmed.ncbi.nlm.nih.gov/39190024/

4. Cai, Xin, Gao, Chengbin, Song, Huanhuan, Tan, Fenghua, Li, Chao. 2018. Characterization, expression profiling and functional characterization of cathepsin Z (CTSZ) in turbot (Scophthalmus maximus L.). In Fish & shellfish immunology, 84, 599-608. doi:10.1016/j.fsi.2018.10.046. https://pubmed.ncbi.nlm.nih.gov/30359754/

5. Li, Wei, Yu, Xinfang, Ma, Xiaolong, Yang, Yifeng, Liu, Haidan. 2018. Deguelin attenuates non-small cell lung cancer cell metastasis through inhibiting the CtsZ/FAK signaling pathway. In Cellular signalling, 50, 131-141. doi:10.1016/j.cellsig.2018.07.001. https://pubmed.ncbi.nlm.nih.gov/30018008/