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The role of kallikreins in inflammatory skin disorders and their potential as therapeutic targets
Critical Reviews in Clinical Laboratory Sciences ( IF 6.6 ) Pub Date : 2020-06-22 , DOI: 10.1080/10408363.2020.1775171
Caitlin T Di Paolo 1, 2 , Eleftherios P Diamandis 1, 2, 3 , Ioannis Prassas 2
Affiliation  

Abstract

The skin is a vital organ of the human body, serving numerous protective and functional roles that are essential for survival. Residing in the epidermis are various epidermal proteases responsible for the establishment and regulation of barrier function. The human tissue kallikrein-related peptidase family conserves homeostasis of the skin barrier through their roles in desquamation, antimicrobial defense, innate immune response, and barrier maintenance. The activity of kallikreins is tightly regulated and dysregulation of kallikrein activity is seen to contribute to the formation of several inflammatory skin disorders. This review highlights the roles of kallikreins in skin homeostasis and pathologies. Due to their part in these skin disorders, inhibitors of the skin kallikreins have become attractive therapeutics. Over the past few years, both natural and synthetic inhibitors of several kallikreins have been identified and are undergoing further development as treatments to restore compromised barrier function. This review summarizes the kallikrein inhibitors under development for this purpose. These inhibitors remain promising therapeutics in cases of severe skin inflammation not well managed by current therapies.



中文翻译:

激肽释放酶在炎症性皮肤病中的作用及其作为治疗靶点的潜力

摘要

皮肤是人体的重要器官,具有多种生存所必需的保护和功能作用。存在于表皮中的是负责建立和调节屏障功能的各种表皮蛋白酶。人体组织激肽释放酶相关肽酶家族通过其在脱屑、抗菌防御、先天免疫反应和屏障维持中的作用来保持皮肤屏障的稳态。激肽释放酶的活性受到严格调控,并且发现激肽释放酶活性的失调会导致多种炎症性皮肤病的形成。这篇综述强调了激肽释放酶在皮肤稳态和病理中的作用。由于它们在这些皮肤病中的作用,皮肤激肽释放酶抑制剂已成为有吸引力的治疗剂。过去几年,几种激肽释放酶的天然和合成抑制剂已被确定,并且正在进一步开发作为恢复受损屏障功能的治疗方法。本综述总结了为此目的而开发的激肽释放酶抑制剂。在当前疗法无法很好控制的严重皮肤炎症的情况下,这些抑制剂仍然是有希望的治疗方法。

更新日期:2020-06-22
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