Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing γ-secretase-independent ERK/CREB signaling.

ABSTRACT: Autophagy 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)-re

SUBMITTER: Chong CM 

PROVIDER: S-EPMC6115391 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature