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- Title
Alzheimer's disease-associated peptide Aβ<sub>42</sub> mobilizes ER Ca<sup>2+</sup> via InsP<sub>3</sub>R-dependent and -independent mechanisms.
- Authors
Jensen, Laura E.; Bultynck, Geert; Luyten, Tomas; Amijee, Hozeefa; Bootman, Martin D.; Roderick, H. Llewelyn
- Abstract
Dysregulation of Ca2+ homeostasis is considered to contribute to the toxic action of the Alzheimer's disease (AD)-associated amyloid-β-peptide (Aβ). Ca2+ fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca2+ fluxes induced by Aβ42. Here, we investigated the contribution of Ca<sup2+</sup release from the endoplasmic reticulum (ER) to the effects of Aβ42 upon Ca2+ homeostasis and the mechanism by which Aβ42 elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ42 induced an elevation in intracellular Ca2+. The Aβ42-stimulated Ca2+ signals persisted in the absence of extracellular Ca2+ indicating a significant contribution of Ca2+ release from the ER Ca2+ store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP3) signaling contributed to Aβ42-stimulated Ca2+ release. The Ca2+ mobilizing effect of Aβ42 was also observed when applied to permeabilized cells deficient in InsP3 receptors, revealing an additional direct effect of Aβ42 upon the ER, and a mechanism for induction of toxicity by intracellular Aβ42.
- Subjects
HOMEOSTASIS; ALZHEIMER'S disease; AMYLOID beta-protein; ENDOPLASMIC reticulum; INOSITOL trisphosphate
- Publication
Frontiers in Molecular Neuroscience, 2013, Vol 6, p1
- ISSN
1662-5099
- Publication type
Article
- DOI
10.3389/fnmol.2013.00036