Investigations of Alzheimer's disease (AD), traumatic brain injury (TBI), and related brain disorders have provided extensive evidence for involvement of cathepsin B, a lysosomal cysteine protease, in mediating the behavioral deficits and neuropathology of these neurodegenerative diseases. This review integrates findings of cathepsin B regulation in clinical biomarker studies, animal model genetic and inhibitor evaluations, structural studies, and lysosomal cell biological mechanisms in AD, TBI, and related brain disorders. The results together indicate the role of cathepsin B in the behavioral deficits and neuropathology of these disorders. Lysosomal leakage occurs in AD and TBI, and related neurodegeneration, which leads to the hypothesis that cathepsin B is redistributed from the lysosome to the cytosol where it initiates cell death and inflammation processes associated with neurodegeneration. These results together implicate cathepsin B as a major contributor to these neuropathological changes and behavioral deficits. These findings support the investigation of cathepsin B as a potential drug target for therapeutic discovery and treatment of AD, TBI, and TBI-related brain disorders.

中文翻译：

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组织蛋白酶 B 在阿尔茨海默病、创伤性脑损伤和相关脑部疾病的神经变性中的作用。

对阿尔茨海默病 (AD)、外伤性脑损伤 (TBI) 和相关脑部疾病的研究为组织蛋白酶 B（一种溶酶体半胱氨酸蛋白酶）参与介导这些神经退行性疾病的行为缺陷和神经病理学提供了广泛的证据。本综述整合了临床生物标志物研究、动物模型遗传和抑制剂评估、结构研究以及 AD、TBI 和相关脑部疾病的溶酶体细胞生物学机制中组织蛋白酶 B 调节的发现。结果共同表明组织蛋白酶 B 在这些疾病的行为缺陷和神经病理学中的作用。溶酶体渗漏发生在 AD 和 TBI 以及相关的神经变性中，这导致假设组织蛋白酶 B 从溶酶体重新分布到细胞质中，在那里它启动与神经变性相关的细胞死亡和炎症过程。这些结果共同表明组织蛋白酶 B 是导致这些神经病理学变化和行为缺陷的主要因素。这些发现支持将组织蛋白酶 B 作为潜在药物靶点的研究，用于 AD、TBI 和 TBI 相关脑部疾病的治疗发现和治疗。