Mezentsev A V, Bruskin S A, Soboleva A G, Sobolev V V, Piruzian E S
Federal Non-profit Research Institute of Russian Academy of Sciences, N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia.
Int J Biomed Sci. 2013 Sep;9(3):112-22.
Receptor for advanced glycation end-products is implicated in a development of chronic inflammatory response. Aim of this paper is to provide a review on commercial and experimental medicines that can interfere with RAGE and signaling through RAGE. We searched three bibliographical databases (PubMed, Web of Science and MEDLINE) for the publications from 2005 to March 2012 and identified 5 major groups of agents that can interfere with RAGE biological effects. In the first part of this paper, we discuss AGE crosslink breakers. These chemicals destroy advanced glycation end products (AGEs) that are crosslinked to the extracellular matrix proteins and can interact with RAGE as ligands. Then, we describe two non-conventional agents SAGEs and KIOM-79 that abolish certain biological effects of RAGE and have a strong anti-inflammatory potential. In the third part, we evaluate the inhibitors of the signaling cascades that underlie RAGE. Particularly, we discuss two groups of kinase inhibitors tyrphostins and the inhibitors of JAK kinases. Considering RAGE as a potential master regulator of processes that are crucial for the pathogenesis of psoriasis, we propose that these medicins may help in controlling the disease by abolishing the chronic inflammation in skin lesions.
晚期糖基化终产物受体与慢性炎症反应的发生有关。本文旨在综述可干扰晚期糖基化终产物受体（RAGE）及其信号传导的商用和实验性药物。我们检索了三个文献数据库（PubMed、科学网和医学期刊数据库），查找2005年至2012年3月期间的相关出版物，确定了5大类可干扰RAGE生物学效应的药物。在本文的第一部分，我们讨论了晚期糖基化终产物交联破坏剂。这些化学物质可破坏与细胞外基质蛋白交联的晚期糖基化终产物（AGEs），并能作为配体与RAGE相互作用。接着，我们描述了两种非传统药物SAGEs和KIOM-¬79，它们可消除RAGE的某些生物学效应，并具有强大的抗炎潜力。在第三部分，我们评估了RAGE信号传导级联反应的抑制剂。特别地，我们讨论了两类激酶抑制剂——酪氨酸磷酸化抑制剂和JAK激酶抑制剂。鉴于RAGE可能是银屑病发病机制中关键过程的潜在主要调节因子，我们认为这些药物可能通过消除皮肤病变中的慢性炎症来帮助控制疾病。
