Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1-42-mediated toxicity.
Activator protein 1
Alzheimer's disease
Aβ 1–42 peptides
Neuronal death
Transglutaminase 1
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
20
12
2019
revised:
01
03
2020
accepted:
24
03
2020
pubmed:
31
3
2020
medline:
9
7
2021
entrez:
31
3
2020
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is the most common cause of dementia. At the pre-symptomatic phase of the disease, the processing of the amyloid precursor protein (APP) produces toxic peptides, called amyloid-β 1-42 (Aβ 1-42). The downstream effects of Aβ 1-42 production are not completely uncovered. Here, we report the involvement of transglutaminase 1 (TG1) in in vitro AD models of neuronal toxicity. TG1 was increased at late stages of the disease in the hippocampus of a mouse model of AD and in primary cortical neurons undergoing stress. Silencing of TGM1 gene was sufficient to prevent Aβ-mediated neuronal death. Conversely, its overexpression enhanced cell death. TGM1 upregulation was mediated at the transcriptional level by an activator protein 1 (AP1) binding site that when mutated halted TGM1 promoter activation. These results indicate that TG1 acts downstream of Aβ-toxicity, and that its stress-dependent increase makes it suitable for pharmacological intervention.
Identifiants
pubmed: 32222473
pii: S0969-9961(20)30124-8
doi: 10.1016/j.nbd.2020.104849
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Peptide Fragments
0
amyloid beta-protein (1-42)
0
Transglutaminases
EC 2.3.2.13
transglutaminase 1
EC 2.3.2.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104849Informations de copyright
Copyright © 2020. Published by Elsevier Inc.