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Upregulation of the sarco-Endoplasmic Reticulum calcium ATPase 1 truncated isoform plays a pathogenic role in Alzheimer’s disease

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Title: Upregulation of the sarco-Endoplasmic Reticulum calcium ATPase 1 truncated isoform plays a pathogenic role in Alzheimer’s disease
Authors: Bussiere
Oulès
Mary
Vaillant-Beuchot
Martin
Manaa
Vallée
Duplan
Paterlini-Bréchot
Costa
Checler
Chami
Item Type: Journal Article
Abstract: Dysregulation of the Endoplasmic Reticulum (ER) Ca2+ homeostasis and subsequent ER stress activation occur in Alzheimer Disease (AD). We studied the contribution of the human truncated isoform of the sarco-endoplasmic reticulum Ca2+ ATPase 1 (S1T) to AD. We examined S1T expression in human AD-affected brains and its functional consequences in cellular and transgenic mice AD models. S1T expression is increased in sporadic AD brains and correlates with amyloid β (Aβ) and ER stress chaperone protein levels. Increased S1T expression was also observed in human neuroblastoma cells expressing Swedish-mutated β-amyloid precursor protein (βAPP) or treated with Aβ oligomers. Lentiviral overexpression of S1T enhances in return the production of APP C-terminal fragments and Aβ through specific increases of β-secretase expression and activity, and triggers neuroinflammation. We describe a molecular interplay between S1T-dependent ER Ca2+ leak, ER stress and βAPP-derived fragments that could contribute to AD setting and/or progression.
Issue Date: 28-Nov-2019
Date of Acceptance: 26-Nov-2019
URI: http://hdl.handle.net/10044/1/76257
DOI: 10.3390/cells8121539
ISSN: 2073-4409
Publisher: MDPI AG
Start Page: 1539
End Page: 1539
Journal / Book Title: Cells
Volume: 8
Issue: 12
Keywords: Alzheimer disease
BACE1
C83
C99
amyloid precursor protein
amyloid β
endoplasmic reticulum stress
neuroinflammation
truncated isoform of the sarco-endoplasmic reticulum Ca2+ ATPase 1 (S1T)
Publication Status: Published
Online Publication Date: 2019-11-28
Appears in Collections:Department of Brain Sciences



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