Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=41341968
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Presenilin 2 regulates corticosterone-induced autophagic death of adult
hippocampal neural stem cells
#MMPMID41341968
Hong J
; An HK
; Nam H
; Choi J
; Yu SW
Anim Cells Syst (Seoul)
2026[]; 30
(1
): 35-46
PMID41341968
show ga
Chronic psychological stress is a well-known risk factor for neurodegenerative
diseases including Alzheimer disease (AD), yet the underlying mechanisms remain
unclear. We previously showed that chronic stress impairs adult hippocampal
neurogenesis by triggering autophagic cell death of adult hippocampal neural stem
(HCN) cells. Impairment of adult hippocampal neurogenesis is widely observed in
the brains of human AD patients and animal models. However, it remains unknown
whether stress-induced death of HCN cells is related to the pathogenesis of AD.
In this study, we investigated whether the stress hormone, corticosterone (CORT)
induces HCN cell death through presenilin 2 (Psen2), a gene associated with
familial AD. Using CRISPR/Cas9-based knockout models and in vitro CORT treatment,
we found that Psen2 expression is upregulated by CORT and Psen2 deletion prevents
CORT-induced death in HCN cells. However, the Psen2 N141I mutation, despite its
pathogenicity in AD, did not exacerbate CORT-induced cell death in vitro and
hippocampus-dependent behavioral deficits in vivo. These findings indicate that
while Psen2 is essential for stress-induced death of HCN cells, the Psen2 N141I
mutation alone may not be sufficient to link chronic stress to AD pathogenesis.
free
free
free
