The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease

KIZ OpenIR

	The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease
	Shen, HT; Xie, YY; Wang, Y; Xie, YS; Wang, YX; Su, ZY; Zhao, LX; Yao, S; Cao, XL; Liang, JL; Long, JR; Zhong, RM; Tang, JF; Wang, SJ; Zhang, LQ; Wang, XJ; Stork, B; Cui, LL; Wu, WX
	2025
发表期刊	AUTOPHAGY
ISSN	1554-8627
摘要	Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux. In the brains of people with AD and APP-PSEN1 mice, the interaction of CANX and ULK1 declines. In mice, the lack of CANX in hippocampal neurons causes the accumulation of autophagy receptors and neuron damage, which affects the cognitive function of C57BL/6 mice. Conversely, overexpression of CANX in hippocampal neurons enhances autophagy flux and partially contributes to improving cognitive function of APP-PSEN1 mice, but not the CANX variant lacking the interaction domain with ULK1. These findings reveal a novel role of CANX in autophagy activity and cognitive function by cooperating with ULK1.Abbreviation: AD: Alzheimer disease; APEX: ascorbate peroxidase; APP: amyloid beta precursor protein; APP-PSEN1 mice: amyloid beta precursor protein-presenilin 1 transgenic mice; ATG: autophagy related; A beta: amyloid-beta; BiFC: bimolecular fluorescence complementation; CANX: calnexin; EBSS: Earle's balanced salt solution; EM: electron microscopy; IP: immunopurification; KO: knockout; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MWM: Morris water maze; PLA: proximity ligation assay; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; SQSTM1/p62, sequestosome 1.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14717
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Shen, HT,Xie, YY,Wang, Y,et al. The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease[J]. AUTOPHAGY,2025.
APA	Shen, HT.,Xie, YY.,Wang, Y.,Xie, YS.,Wang, YX.,...&Wu, WX.(2025).The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.AUTOPHAGY.
MLA	Shen, HT,et al."The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease".AUTOPHAGY (2025).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
QT2025041036.pdf（13738KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文