Cathepsin D-Managing the Delicate Balance.

Cathepsin D-Managing the Delicate Balance.
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DOI:
10.3390/pharmaceutics13060837
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发表时间:
2021-06-05
期刊:
影响因子:
5.4
通讯作者:
Zamyatnin AA Jr
Zamyatnin AA Jr
中科院分区:
医学2区
文献类型:
--
作者:
Mijanovic O;Petushkova AI;Brankovic A;Turk B;Solovieva AB;Nikitkina AI;Bolevich S;Timashev PS;Parodi A;Zamyatnin AA Jr

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溶酶体蛋白酶在维持细胞内稳态中起着至关重要的作用。人组织蛋白酶D管理蛋白质周转,降解错误折叠和聚集的蛋白质,并在蛋白质稳态破坏的情况下促进细胞凋亡。然而,当组织蛋白酶D调节受到影响时,它可以导致许多疾病。人组织蛋白酶D的下调与神经退行性疾病,如神经元蜡样脂褐质沉积症有关。另一方面,其在溶酶体和细胞膜外的过量水平导致肿瘤生长、迁移、侵袭和血管生成。因此,靶向组织蛋白酶D可以提供显著的诊断益处和新的治疗途径。在此,我们提供了一个简要的概述组织蛋白酶D的结构,调节,功能,其在许多疾病的进展和治疗潜力的天然和合成的抑制剂和激活剂,这种蛋白酶的作用。
Lysosomal proteases play a crucial role in maintaining cell homeostasis. Human cathepsin D manages protein turnover degrading misfolded and aggregated proteins and favors apoptosis in the case of proteostasis disruption. However, when cathepsin D regulation is affected, it can contribute to numerous disorders. The down-regulation of human cathepsin D is associated with neurodegenerative disorders, such as neuronal ceroid lipofuscinosis. On the other hand, its excessive levels outside lysosomes and the cell membrane lead to tumor growth, migration, invasion and angiogenesis. Therefore, targeting cathepsin D could provide significant diagnostic benefits and new avenues of therapy. Herein, we provide a brief overview of cathepsin D structure, regulation, function, and its role in the progression of many diseases and the therapeutic potentialities of natural and synthetic inhibitors and activators of this protease.
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