Glutaminyl Cyclase, Diseases, and Development of Glutaminyl Cyclase Inhibitors
Glutaminyl Cyclase, Diseases, and Development of Glutaminyl Cyclase Inhibitors
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DOI：
10.1021/acs.jmedchem.1c00325
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发表时间：
2021-05-18
影响因子：
7.3
通讯作者：
Wu，Haiqiang
中科院分区：
文献类型：
--
作者：
Xu，Chenshu;Wang，Yi-nan;Wu，Haiqiang
焦谷氨酸(Pe)修饰主要由谷氨酰环酶(QC)催化，广泛存在于自然界，在包括人类在内的哺乳动物体内对激素、多肽和蛋白质的成熟起着特别重要的作用。在人类中，QC的上调与多种疾病和条件有关，包括阿尔茨海默病、亨廷顿病、黑色素瘤、甲状腺癌、加速的动脉粥样硬化、感染性关节炎等。这种上调催化了修饰介质的生成，如PE-淀粉样β蛋白(A？)和PE-趋化因子配体2(CCL2)。不足为奇的是，QC已经成为对抗这些疾病和状况的治疗学发展的合理目标。本文综述了QC上调导致疾病表现的危害，以及QC抑制剂的研究进展。
Pyroglutamate (pE) modification, catalyzed mainly by glutaminyl cyclase (QC), is prevalent throughout nature and is particularly important in mammals including humans for the maturation of hormones, peptides, and proteins. In humans, the upregulation of QC is involved in multiple diseases and conditions including Alzheimer’s disease, Huntington’s disease, melanomas, thyroid carcinomas, accelerated atherosclerosis, septic arthritics, etc. This upregulation catalyzes the generation of modified mediators such as pE-amyloid beta (Aß) and pE-chemokine ligand 2 (CCL2) peptides. Not surprisingly, QC has emerged as a reasonable target for the development of therapeutics to combat these diseases and conditions. In this manuscript the deleterious effects of upregulated QC resulting in disease manifestation are reviewed, along with progress on the development of QC inhibitors.