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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 |