Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing, China.
Department of Medical Genetics & Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Brain Pathol. 2022 Sep;32(5):e13071. doi: 10.1111/bpa.13071. Epub 2022 Apr 12.
Cathepsin B (CatB) is a typical cysteine lysosomal protease involved in a variety of physiologic and pathological processes. It is expressed in most cell types and is primarily localized within subcellular endosomal and lysosomal compartments. Emerging scientific evidence indicates that lysosomal leaked CatB is involved in mitochondrial stress, inflammasome activation, and nuclear senescence, but without the acidic environment. CatB is also secreted as a myokine, which is involved in muscle-brain cross talk and neuronal dendritic remodeling. Lysosomal-leaked and cellular-secreted CatB functions are dependent on its enzymatic activity at a neutral pH. In the present review, we summarize the available experimental evidence that mechanistically links extralysosomal CatB to physiological and pathological functions in central nervous system, and their potential for use in therapeutic approaches.
组织蛋白酶 B（CatB）是一种典型的半胱氨酸溶酶体蛋白酶，参与多种生理和病理过程。它在大多数细胞类型中表达，并主要定位于细胞内体和溶酶体隔室中。新出现的科学证据表明，溶酶体漏出的 CatB 参与线粒体应激、炎性体激活和核衰老，但不需要酸性环境。CatB 也作为肌因子分泌，参与肌肉-大脑通讯和神经元树突状重塑。溶酶体漏出和细胞分泌的 CatB 功能依赖于其在中性 pH 值下的酶活性。在本综述中，我们总结了现有的实验证据，这些证据从机制上把细胞外的 CatB 与中枢神经系统的生理和病理功能联系起来，并探讨了它们在治疗方法中的潜在应用。
