Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications.
Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications.
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DOI：
10.1111/bpa.13071
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发表时间：
2022-09
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--
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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，并且主要位于亚细胞内体和溶酶体区室中。新的科学证据表明，溶酶体泄漏的 CatB 与线粒体应激、炎性体激活和核衰老有关，但与酸性环境无关。 CatB 还以肌因子的形式分泌，参与肌脑串扰和神经元树突重塑。溶酶体渗漏和细胞分泌的 CatB 功能取决于其在中性 pH 下的酶活性。在本综述中，我们总结了现有的实验证据，这些证据在机制上将溶酶体外 CatB 与中枢神经系统的生理和病理功能联系起来，及其在治疗方法中使用的潜力。新的科学证据表明，溶酶体泄漏的 CatB 与线粒体应激、炎性体激活和核衰老有关，但与酸性环境无关。 CatB 还以肌因子的形式分泌，参与肌脑串扰和神经元树突重塑。在本综述中，我们总结了现有的实验证据，这些证据在机制上将溶酶体外 CatB 与中枢神经系统的生理和病理功能联系起来，及其在治疗方法中使用的潜力
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. 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. 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
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