遗传 ›› 2023, Vol. 45 ›› Issue (3): 212-220.doi: 10.16288/j.yczz.22-422
商晓康(
), 张思萌(), 倪军军()
收稿日期:2022-12-26
修回日期:2023-02-15
出版日期:2023-03-20
发布日期:2023-02-21
通讯作者:
倪军军
E-mail:1120202339@bit.edu.cn;zhangsimeng0301@163.com;nijunjun@bit.edu.cn
作者简介:商晓康，在读本科生，专业方向：生物技术。E-mail: 基金资助:
Xiaokang Shang(), Simeng Zhang(), Junjun Ni()
Received:2022-12-26
Revised:2023-02-15
Online:2023-03-20
Published:2023-02-21
Contact:
Ni Junjun
E-mail:1120202339@bit.edu.cn;zhangsimeng0301@163.com;nijunjun@bit.edu.cn
Supported by:摘要：
组织蛋白酶B (cathepsin B，CatB)是一种定位于溶酶体的半胱氨酸蛋白酶，最初被认为在溶酶体内发挥非选择性地降解吞噬或者自噬蛋白的功能。然而最新研究发现，CatB也可以选择性地降解或特异性地活化目标蛋白，从而参与调控生理病理反应。在衰老及相关的神经退行性疾病的大脑中，CatB的表达、酶活性及细胞定位都发生了显著变化，因此CatB在衰老和神经退行性疾病中的病理学功能备受关注。本文对CatB参与脑衰老及阿尔兹海默症进程的相关研究进行了系统梳理，并讨论了目前有关CatB的神经病理学研究中存在的问题，以期为全面认识脑衰老及阿尔兹海默症的病理机制奠定基础。
商晓康, 张思萌, 倪军军. 组织蛋白酶B参与脑衰老及阿尔兹海默症发生发展研究进展[J]. 遗传, 2023, 45(3): 212-220.
Xiaokang Shang, Simeng Zhang, Junjun Ni. Research progress of cathepsin B in brain aging and Alzheimer’s diseases[J]. Hereditas(Beijing), 2023, 45(3): 212-220.
图1
CatB在细胞器中的转移及成熟过程 在内质网中，CatB酶原被切除信号肽且被糖基化；随后转移到高尔基体，CatB前体的甘露糖残基被磷酸化后，与内体中甘露糖-6磷酸化受体结合，并进一步在溶酶体酸性环境中发生前体自切割，形成CatB成熟体。"
图2
CatB在脑衰老及AD病理中的功能 在大脑中，CatB分别在小胶质细胞和神经元中表达。在小胶质细胞中，CatB介导NLRP3炎症小体激活、细胞凋亡和氧化应激；在神经元中，CatB会破坏神经发生和突触可塑性，并且对β淀粉样蛋白有影响，但是CatB对β淀粉样蛋白诱导或清除的研究还未形成统一的结论。"
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