2011年7月20日 · Genetic ablation of the glutaminyl cyclase iso‐enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE 1 ‐CCL2 formation and monocyte infiltration. Consistently, administration of QC‐inhibitors in inflammatory models, such as thioglycollate‐induced peritonitis reduced monocyte infiltration.

The expression of QC/isoQC is upregulated by proinflammatory cytokines such as CCL2 and CX3C chemokine ligand 1 (CX3CL1), which act as its substrates. CCL2 is a chemokine known to recruit monocytes to sites of inflammation, playing important roles in cancer progression .

2023年10月1日 · In addition, the pE-modification of C-C motif chemokine ligand (CCL)-2 by QPCTL will also upregulate local CCL2 expression, which might, in turn, induce proinflammatory responses by activating the CCR2 receptor, causing neurotoxicity and inflammation, ultimately exacerbating AD progression.

2022年9月15日 · QC inhibitor SEN177 could block the interaction of CD47-SIRPα axis. sQC promotes the stability of HRAS and reduces its ubiquitination-mediated degradation, leading to Sunitinib resistance in RCC. Pyroglutamate modification of CCL2 leads to a higher level of CCL2, which can recruit more monocytes, memory T cells and dendritic cells into the TME.

在本文中，团队总结了CCL2-CCR2信号轴在肿瘤发生发展中的作用，并重点介绍了其靶向治疗肿瘤的最新研究，尤其针对临床前研究和临床试验。 趋化因子是小分子蛋白，其通过与细胞表面 G蛋白偶联趋化因子受体 （GPCR）结合来发挥其功能。 迄今为止，已在人类中鉴定出超过50种趋化因子和19种不同的趋化因子受体，根据N端保守半胱氨酸残基的数量和间距，趋化因子分为四个主要亚家族：CXC、CC、C和CX3C，大多数趋化因子属于CC和CXC亚家族。 在CC亚家族 …

2024年1月1日 · The presence of pE considerably prolongs the in vivo half-life of CCL2 and enhances the recognition and binding of CCL2 and CCL2 receptor, causing excessive inflammation. Crucially, the generation of both pE-Aβ and pE-CCL2 is mainly catalyzed by QC, and QC is significantly upregulated in the brains of people with AD during the early stages of ...

2021年5月17日 · 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 …

2024年8月23日 · In parallel, immunohistochemical signals for the QC substrate CCL2 increased from 24 to 72 h after ischemia induction without differences between genotypes analyzed. The increase in CCL2 was accompanied by morphological activation of Iba1-immunoreactive microglia and recruitment of MHC-II-positive cells at 72 h after ischemia.

Application of a QC/isoQC inhibitor led to a significant reduction in circulating alanine aminotransferase and NAFLD activity score accompanied by an inhibitory effect on hepatocyte ballooning. Further analysis revealed a specific reduction of inflammation by decreasing the number of F4/80-positive macrophages, which is in agreement with the ...

2021年3月29日 · The N-terminal glutamine on immature CCL2 is replaced with pyroglutamate (pE) by glutaminyl cyclase (QC) and isoQC. pE-CCL2 is stable and resistant to peptidases. We hypothesized that inhibiting QC/isoQC activity would lead to the degradation of CCL2, thereby ameliorating CKD and reducing kidney inflammation.