CSpace  > 2018期刊论文
Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing gamma-secretase-independent ERK/CREB signaling
Chong, Cheong-Meng; Ke, Minjing; Tan, Yuan; Huang, Zhijian; Zhang, Ke; Ai, Nana; Ge, Wei; Qin, Dajiang; Lu, Jia-Hong; Su, Huanxing
2019-08-29
Source PublicationCELL DEATH & DISEASE
Volume9
AbstractAutophagy impairment is commonly implicated in the pathological characteristic of Alzheimer's disease (AD). Presenilin 1 (PS1) expression in human brain gradually decreases with age and its mutations account for the most common cases of early-onset familial Alzheimer's disease (FAD). The dominant autophagy phenotypes occur in PS1-knockout and PS1 mutant neurons; it is still unknown whether PS1 deficiency causes serious autophagy impairment in neural stem cells (NSCs). Herein, we generated the heterozygote and homozygote of PS1 knockout in human induced pluripotent stem cells (iPSCs) via CRISPR/Cas9-based gene editing and differentiated them into human NSCs. In these human PS1-deficient NSCs, reduced autophagosome formation and downregulated expression of autophagy-lysosome pathway (ALP)-related mRNAs, as well as proteins were observed. Mechanistically, ERK/CREB inhibition and GSK3 beta activation had key roles in reducing TFEB expression in PS1-knockout NSCs. Pharmacological inhibition of GSK3 beta upregulated the expression of TFEB and ALP-related proteins in PS1-knockout NSCs, whereas this effect could be blocked by CREB inhibition. These findings demonstrate that PS1 deficiency causes autophagy suppression in human NSCs via downregulating ERK/CREB signaling.
Indexed BySCIE
Document Type期刊论文
Identifierhttp://ir.foo.ac.cn/handle/2SETSVCV/1472
Collection2018期刊论文
Recommended Citation
GB/T 7714
Chong, Cheong-Meng,Ke, Minjing,Tan, Yuan,et al. Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing gamma-secretase-independent ERK/CREB signaling[J]. CELL DEATH & DISEASE,2019,9.
APA Chong, Cheong-Meng.,Ke, Minjing.,Tan, Yuan.,Huang, Zhijian.,Zhang, Ke.,...&Su, Huanxing.(2019).Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing gamma-secretase-independent ERK/CREB signaling.CELL DEATH & DISEASE,9.
MLA Chong, Cheong-Meng,et al."Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing gamma-secretase-independent ERK/CREB signaling".CELL DEATH & DISEASE 9(2019).
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