Neuronal C/EBPβ/AEP pathway shortens life span via selective GABAnergic neuronal degeneration by FOXO repression.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
entrez:
30
3
2022
pubmed:
31
3
2022
medline:
2
4
2022
Statut:
ppublish
Résumé
The age-related cognitive decline of normal aging is exacerbated in neurodegenerative diseases including Alzheimer's disease (AD). However, it remains unclear whether age-related cognitive regulators in AD pathologies contribute to life span. Here, we show that C/EBPβ, an Aβ and inflammatory cytokine-activated transcription factor that promotes AD pathologies via activating asparagine endopeptidase (AEP), mediates longevity in a gene dose-dependent manner in neuronal C/EBPβ transgenic mice. C/EBPβ selectively triggers inhibitory GABAnergic neuronal degeneration by repressing FOXOs and up-regulating AEP, leading to aberrant neural excitation and cognitive dysfunction. Overexpression of CEBP-2 or LGMN-1 (AEP) in
Identifiants
pubmed: 35353567
doi: 10.1126/sciadv.abj8658
pmc: PMC8967231
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabj8658Subventions
Organisme : NIA NIH HHS
ID : P30 AG072975
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065177
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG069042
Pays : United States
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