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
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

eabj8658

Subventions

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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Auteurs

Yiyuan Xia (Y)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Hiroshi Qadota (H)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Zhi-Hao Wang (ZH)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Pai Liu (P)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Neuroscience program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA.

Xia Liu (X)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Karen X Ye (KX)

Emory College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA.

Courtney J Matheny (CJ)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Ken Berglund (K)

Department of Neurosurgery, Emory University, Atlanta, GA 30322, USA.

Shan Ping Yu (SP)

Department of Anesthesiology, Emory University, Atlanta, GA 30322, USA.

Derek Drake (D)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

David A Bennett (DA)

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Xiao-Chuan Wang (XC)

Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China.

Bruce A Yankner (BA)

Department of Genetics, Harvard Medical School, Boston, MA, USA.

Guy M Benian (GM)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.

Keqiang Ye (K)

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Shenzhen, China.

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Classifications MeSH