[en] Dysregulation of the Endoplasmic Reticulum (ER) Ca(2+) 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 Ca(2+) 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 Ca(2+) leak, ER stress and βAPP-derived fragments that could contribute to AD setting and/or progression.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bussiere, Renaud
Oulès, Bénédicte
MARY, Arnaud ; Université Côte d'Azur, INSERM, CNRS, IPMC, France, Laboratory of excellence DistALZ, 660 route des Lucioles,6560, Sophia-Antipolis, Valbonne, France
Vaillant-Beuchot, Loan
Martin, Cécile
El Manaa, Wejdane
Vallée, Déborah
Duplan, Eric
Paterlini-Bréchot, Patrizia
Alves Da Costa, Cristine
Checler, Frédéric
Chami, Mounia
External co-authors :
no
Language :
English
Title :
Upregulation of the Sarco-Endoplasmic Reticulum Calcium ATPase 1 Truncated Isoform Plays a Pathogenic Role in Alzheimer's Disease.
Publication date :
2019
Journal title :
Cells
eISSN :
2073-4409
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Basel, Switzerland