Article (Scientific journals)
Upregulation of the Sarco-Endoplasmic Reticulum Calcium ATPase 1 Truncated Isoform Plays a Pathogenic Role in Alzheimer's Disease.
Bussiere, Renaud; Oulès, Bénédicte; Mary, Arnaud et al.
2019In Cells, 8 (12)
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Keywords :
Aged; Aged, 80 and over; Alzheimer Disease/genetics/metabolism/pathology; Amyloid Precursor Protein Secretases/metabolism; Amyloid beta-Peptides/metabolism; Amyloid beta-Protein Precursor/metabolism; Animals; Biomarkers; Brain/metabolism/pathology; Cell Line; Disease Models, Animal; Disease Susceptibility; Endoplasmic Reticulum Stress; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Inflammation Mediators/metabolism; Isoenzymes; Male; Mice; Mice, Transgenic; Middle Aged; Models, Biological; Protein Aggregation, Pathological; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics/metabolism; Signal Transduction; Alzheimer disease; BACE1; C83; C99; amyloid precursor protein; amyloid β; neuroinflammation; truncated isoform of the sarco-endoplasmic reticulum Ca2+ ATPase 1 (S1T)
Abstract :
[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, 06560, 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 :
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Title :
Upregulation of the Sarco-Endoplasmic Reticulum Calcium ATPase 1 Truncated Isoform Plays a Pathogenic Role in Alzheimer's Disease.
Publication date :
Journal title :
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Basel, Switzerland
Volume :
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Peer reviewed :
Peer Reviewed verified by ORBi
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since 12 September 2023


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