谷氨酰胺合成酶
谷氨酸受体
兴奋毒性
化学
内科学
内分泌学
谷氨酰胺
神经科学
医学
生物化学
生物
氨基酸
受体
作者
Yanlan Long,Zhihui Zhao,Weiping Xie,Jing Shi,Fang Yang,Dan Zhu,Ping Jiang,Qing Tang,Ti Zhou,Bin Jiang,Xia Yang,Guoquan Gao,Weiwei Qi
标识
DOI:10.1016/j.phrs.2024.107145
摘要
In many neurodegenerative disorders, such as Alzheimer's disease (AD), glutamate-mediated neuronal excitotoxicity is considered the basis for cognitive impairment. The mRNA and protein expression of SERPINA4(Kallistatin) are higher in patients with AD. However, whether Kallistatin plays a regulatory role in glutamate-glutamine cycle homeostasis remains unclear. In this study, we identified impaired cognitive function in Kallistatin transgenic (KAL-TG) mice. Baseline glutamate levels were elevated and miniature excitatory postsynaptic current (mEPSC) frequency was increased in the hippocampus, suggesting the impairment of glutamate homeostasis in KAL-TG mice. Mechanistically, we demonstrated that Kallistatin promoted lysine acetylation and ubiquitination of glutamine synthetase (GS) and facilitated its degradation via the proteasome pathway, thereby downregulating GS. Fenofibrate improved cognitive memory in KAL-TG mice by downregulating serum Kallistatin. Collectively, our study findings provide insights the mechanism by which Kallistatin regulates cognitive impairment, and suggest the potential of fenofibrate to prevente and treat of AD patients with high levels of Kallistatin.
科研通智能强力驱动
Strongly Powered by AbleSci AI