Δ133p53α Protects Human Astrocytes from Amyloid-beta Induced Senescence and Neurotoxicity.
Alzheimer’s
DNA damage
SASP
p53
p53 isoforms
Journal
Neuroscience
ISSN: 1873-7544
Titre abrégé: Neuroscience
Pays: United States
ID NLM: 7605074
Informations de publication
Date de publication:
21 08 2022
21 08 2022
Historique:
received:
03
09
2021
revised:
26
05
2022
accepted:
01
06
2022
pubmed:
19
6
2022
medline:
31
8
2022
entrez:
18
6
2022
Statut:
ppublish
Résumé
Cellular senescence is an important contributor to aging and age-related diseases such as Alzheimer's disease (AD). Senescent cells are characterized by a durable cell proliferation arrest and the acquisition of a proinflammatory senescence-associated secretory phenotype (SASP), which participates in the progression of neurodegenerative disorders. Clearance of senescent glial cells in an AD mouse model prevented cognitive decline suggesting pharmacological agents targeting cellular senescence might provide novel therapeutic approaches for AD. Δ133p53α, a natural protein isoform of p53, was previously shown to be a negative regulator of cellular senescence in primary human astrocytes, with clinical implications from its diminished expression in brain tissues from AD patients. Here we show that treatment of proliferating human astrocytes in culture with amyloid-beta oligomers (Aβ), an endogenous pathogenic agent of AD, results in reduced expression of Δ133p53α, as well as induces the cells to become senescent and express proinflammatory SASP cytokines such as IL-6, IL-1β and TNFα. Our data suggest that Aβ-induced astrocyte cellular senescence is associated with accelerated DNA damage, and upregulation of full-length p53 and its senescence-inducing target gene p21
Identifiants
pubmed: 35716965
pii: S0306-4522(22)00289-5
doi: 10.1016/j.neuroscience.2022.06.004
pmc: PMC9420812
mid: NIHMS1816615
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
190-202Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011496
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
Références
Nat Rev Cancer. 2008 Jul;8(7):512-22
pubmed: 18574463
Cell Res. 2015 Mar;25(3):351-69
pubmed: 25698579
Cancer Lett. 2002 May 8;179(1):1-14
pubmed: 11880176
Front Mol Neurosci. 2017 Dec 19;10:427
pubmed: 29311817
Arch Biochem Biophys. 2007 Jul 15;463(2):245-52
pubmed: 17502108
FASEB J. 2005 Feb;19(2):255-7
pubmed: 15548589
Epigenetics. 2010 Feb 16;5(2):129-36
pubmed: 20150765
Biochim Biophys Acta. 2011 Nov;1812(11):1359-70
pubmed: 21871956
Genes Dev. 2012 May 1;26(9):891-907
pubmed: 22549954
Genes Dev. 2005 Sep 15;19(18):2122-37
pubmed: 16131611
Nat Neurosci. 2019 May;22(5):719-728
pubmed: 30936558
PLoS One. 2015 May 08;10(5):e0125217
pubmed: 25954815
Nat Commun. 2014 Aug 21;5:4706
pubmed: 25144556
J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):575-84
pubmed: 16799139
Int J Cancer. 2012 Apr 15;130(8):1715-25
pubmed: 22025288
J Neural Transm (Vienna). 2018 Feb;125(2):177-191
pubmed: 29196815
Cell Death Differ. 2016 Sep 1;23(9):1515-28
pubmed: 27104929
Neurology. 2013 May 7;80(19):1778-83
pubmed: 23390181
Nat Protoc. 2009;4(12):1798-806
pubmed: 20010931
Am J Pathol. 1998 Jun;152(6):1633-40
pubmed: 9626067
Neuromolecular Med. 2010 Mar;12(1):1-12
pubmed: 20232515
Age (Dordr). 2008 Dec;30(4):209-15
pubmed: 19424844
PLoS One. 2012;7(9):e45069
pubmed: 22984612
Acta Naturae. 2018 Jan-Mar;10(1):4-14
pubmed: 29713514
Cancers (Basel). 2020 Nov 18;12(11):
pubmed: 33218139
J Biol Chem. 2003 Mar 28;278(13):11612-22
pubmed: 12499373
Cell Death Differ. 2017 Jun;24(6):1017-1028
pubmed: 28362428
Exp Gerontol. 2015 Aug;68:3-7
pubmed: 25281806
Aging Cell. 2019 Jun;18(3):e12937
pubmed: 30815970
Cell Cycle. 2017 Sep 17;16(18):1631-1632
pubmed: 28727499
Neuro Oncol. 2019 Mar 18;21(4):474-485
pubmed: 30615147
Biochem Biophys Res Commun. 1997 Mar 17;232(2):418-21
pubmed: 9125193
Immunity. 2017 Jun 20;46(6):957-967
pubmed: 28636962
Science. 1994 Sep 2;265(5177):1464-7
pubmed: 8073293
Nat Neurosci. 2021 Mar;24(3):312-325
pubmed: 33589835
Nature. 2018 Oct;562(7728):578-582
pubmed: 30232451
Curr Alzheimer Res. 2009 Feb;6(1):36-47
pubmed: 19199873
Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a001883
pubmed: 20066118
Nat Cell Biol. 2009 Sep;11(9):1135-42
pubmed: 19701195
Oncogene. 2018 May;37(18):2379-2393
pubmed: 29429991
J Neurochem. 2001 Apr;77(1):220-8
pubmed: 11279278
Trends Biochem Sci. 2009 Jan;34(1):6-8
pubmed: 19008105
Exp Neurol. 2012 Jul;236(1):1-5
pubmed: 22575598
J Neurosci. 2008 Nov 19;28(47):12163-75
pubmed: 19020010