Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
Pharmacol Res. 2019 Sep;147:104342. doi: 10.1016/j.phrs.2019.104342. Epub 2019 Jul 6.
Human glutaminyl cyclase (hQC) is an important enzyme for post-translational modification by converting the N-terminal glutaminyl and glutamyl into pyroglutamate (pGlu) through cyclization. The two isoforms of hQC, secretory glutaminyl cyclase (sQC) and golgi resident glutaminyl cyclase (gQC), are involved in various pathological conditions especially in Alzheimer's disease (AD). The sQC is known to mediate the formation of pyroglutamate containing amyloid beta (pGlu-Aβ) peptides while gQC mediates the maturation of C-C motif chemokine ligand 2 (CCL2). Therefore, hQC (both sQC and gQC) inhibition is considered to be an attractive strategy to prevent the formation of pGlu-Aβ and to reduce neuroinflammation and hence provides a new opportunity for the treatment of AD. In this review, we summarize our current understanding on the structure, function and inhibitors of hQC and its involvement in Alzheimer's disease.
人谷氨酰胺酰环化酶（hQC）是一种通过环化将 N 端谷氨酰胺和谷氨酸转化为焦谷氨酸（pGlu）的重要翻译后修饰酶。hQC 的两种同工酶，分泌型谷氨酰胺酰环化酶（sQC）和高尔基体驻留谷氨酰胺酰环化酶（gQC），参与了各种病理状况，特别是阿尔茨海默病（AD）。已知 sQC 介导含有焦谷氨酸的淀粉样β（pGlu-Aβ）肽的形成，而 gQC 介导 C-C 基序趋化因子配体 2（CCL2）的成熟。因此，hQC（sQC 和 gQC 两者）的抑制被认为是预防 pGlu-Aβ形成和减少神经炎症的一种有吸引力的策略，从而为 AD 的治疗提供了新的机会。在这篇综述中，我们总结了我们目前对 hQC 的结构、功能和抑制剂及其在阿尔茨海默病中的作用的理解。
