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组织蛋白酶 K 在病理条件下的作用及新的治疗和诊断前景。

Cathepsin K in Pathological Conditions and New Therapeutic and Diagnostic Perspectives.

机构信息

Dia-M, LCC, 7 b.3 Magadanskaya Str., 129345 Moscow, Russia.

The Human Pathology Department, Sechenov First Moscow State University, 119991 Moscow, Russia.

出版信息

Int J Mol Sci. 2022 Nov 9;23(22):13762. doi: 10.3390/ijms232213762.

Abstract

Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.

摘要

组织蛋白酶 K(CatK)属于半胱氨酸蛋白酶家族的一部分,参与许多重要的过程,包括骨吸收过程中胶原蛋白 1 和弹性蛋白的降解活性。CatK 水平的变化与各种病理状况有关,主要与骨和软骨降解有关,如多发性骨纤维发育不良(与 CatK 缺乏有关)、骨质疏松症和骨关节炎(与 CatK 过表达有关)。最近,CatK 的分泌增加与血管炎症、过敏性肺炎、韦格纳肉芽肿、铍病、结核病以及肿瘤进展高度相关。由于 CatK 涉及广泛的疾病,因此,近几十年来,活性位点特异性抑制剂的设计和验证一直是制药公司关注的焦点。在这篇综述中,我们总结了 CatK 的分子背景及其在各种疾病中的作用,以及其在诊断和治疗中的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/703f/9698382/31ffde87ab44/ijms-23-13762-g001.jpg

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