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J Neurosci
2013 Feb 27;339:3824-33. doi: 10.1523/JNEUROSCI.4367-12.2013.
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Cytotoxicity of intracellular aβ42 amyloid oligomers involves Ca2+ release from the endoplasmic reticulum by stimulated production of inositol trisphosphate.
Demuro A
,
Parker I
.
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Oligomeric forms of β-amyloid (Aβ(42)) peptides associated with Alzheimer's disease (AD) disrupt cellular Ca(2+) regulation by liberating Ca(2+) into the cytosol from both extracellular and intracellular sources. We elucidated the actions of intracellular Aβ by imaging Ca(2+) responses to injections of Aβ oligomers into Xenopus oocytes. Two types of signal were observed: (1) local, "channel-like" transients dependent on extracellular Ca(2+) influx, which resembled signals from amlyoid pores formed by extracellular application of oligomers; and (2) local transients and global Ca(2+) waves, resembling Ca(2+) puffs and waves mediated by inositol trisphosphate (IP(3)). The latter responses were suppressed by antagonists of the IP(3) receptor (caffeine and heparin), pretreatment with the G(i)(o)-protein inhibitor pertussis toxin, and pretreatment with lithium to deplete membrane inositol lipids. We show that G-protein-mediated stimulation of IP(3) production and consequent liberation of Ca(2+) from the endoplasmic reticulum by intracellular Aβ oligomers is cytotoxic, potentially representing a novel pathological mechanism in AD which may be further exacerbated by AD-linked mutations in presenilins to promote opening of IP(3) receptor/channels.
Alberdi,
Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors.
2010, Pubmed
Alberdi,
Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors.
2010,
Pubmed
Arispe,
Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [A beta P-(1-40)] in bilayer membranes.
1993,
Pubmed
Berridge,
Neuronal calcium signaling.
1998,
Pubmed
Berridge,
Neural and developmental actions of lithium: a unifying hypothesis.
1989,
Pubmed
Berridge,
Calcium hypothesis of Alzheimer's disease.
2010,
Pubmed
Bezprozvanny,
Caffeine-induced inhibition of inositol(1,4,5)-trisphosphate-gated calcium channels from cerebellum.
1994,
Pubmed
Bezprozvanny,
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
2008,
Pubmed
Bezprozvanny,
Calcium signaling and neurodegenerative diseases.
2009,
Pubmed
Cahalan,
STIMulating store-operated Ca(2+) entry.
2009,
Pubmed
Callamaras,
Activation and co-ordination of InsP3-mediated elementary Ca2+ events during global Ca2+ signals in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Dascal,
Types of muscarinic response in Xenopus oocytes.
1980,
Pubmed
,
Xenbase
De Felice,
Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine.
2007,
Pubmed
Demuro,
Calcium signaling and amyloid toxicity in Alzheimer disease.
2010,
Pubmed
Demuro,
Single-channel Ca(2+) imaging implicates Aβ1-42 amyloid pores in Alzheimer's disease pathology.
2011,
Pubmed
,
Xenbase
Demuro,
Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers.
2005,
Pubmed
Deshpande,
Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons.
2006,
Pubmed
Ferreiro,
Involvement of endoplasmic reticulum Ca2+ release through ryanodine and inositol 1,4,5-triphosphate receptors in the neurotoxic effects induced by the amyloid-beta peptide.
2004,
Pubmed
Foskett,
Inositol trisphosphate receptor Ca2+ release channels in neurological diseases.
2010,
Pubmed
Gafni,
Xestospongins: potent membrane permeable blockers of the inositol 1,4,5-trisphosphate receptor.
1997,
Pubmed
Gouras,
Intraneuronal Abeta42 accumulation in human brain.
2000,
Pubmed
Green,
Linking calcium to Abeta and Alzheimer's disease.
2008,
Pubmed
Haass,
Amyloid beta-peptide is produced by cultured cells during normal metabolism.
1992,
Pubmed
Hartmann,
Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides.
1997,
Pubmed
Harwood,
Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited.
2005,
Pubmed
Hertel,
Inhibition of the electrostatic interaction between beta-amyloid peptide and membranes prevents beta-amyloid-induced toxicity.
1997,
Pubmed
Jarrett,
Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?
1993,
Pubmed
Kayed,
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.
2003,
Pubmed
Khachaturian,
Calcium, membranes, aging, and Alzheimer's disease. Introduction and overview.
1989,
Pubmed
Khachaturian,
Calcium hypothesis of Alzheimer's disease and brain aging.
1994,
Pubmed
Kim,
Sequence determinants of enhanced amyloidogenicity of Alzheimer A{beta}42 peptide relative to A{beta}40.
2005,
Pubmed
Knobloch,
Intracellular Abeta and cognitive deficits precede beta-amyloid deposition in transgenic arcAbeta mice.
2007,
Pubmed
Lin,
Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology.
2001,
Pubmed
Mason,
Distribution and fluidizing action of soluble and aggregated amyloid beta-peptide in rat synaptic plasma membranes.
1999,
Pubmed
Miledi,
Latencies of membrane currents evoked in Xenopus oocytes by receptor activation, inositol trisphosphate and calcium.
1989,
Pubmed
,
Xenbase
Moriarty,
Coupling of exogenous receptors to phospholipase C in Xenopus oocytes through pertussis toxin-sensitive and -insensitive pathways. Cross-talk through heterotrimeric G-proteins.
1989,
Pubmed
,
Xenbase
Noh,
Different signaling pathway between sphingosine-1-phosphate and lysophosphatidic acid in Xenopus oocytes: functional coupling of the sphingosine-1-phosphate receptor to PLC-xbeta in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Oddo,
Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.
2003,
Pubmed
Parker,
Caffeine inhibits inositol trisphosphate-mediated liberation of intracellular calcium in Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Parys,
Isolation, characterization, and localization of the inositol 1,4,5-trisphosphate receptor protein in Xenopus laevis oocytes.
1992,
Pubmed
,
Xenbase
Pollard,
A new hypothesis for the mechanism of amyloid toxicity, based on the calcium channel activity of amyloid beta protein (A beta P) in phospholipid bilayer membranes.
1993,
Pubmed
Quist,
Amyloid ion channels: a common structural link for protein-misfolding disease.
2005,
Pubmed
Simakova,
Fluorescent analysis of the cell-selective Alzheimer's disease aβ Peptide surface membrane binding: influence of membrane components.
2011,
Pubmed
Sims,
Metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate by the oocytes of Xenopus laevis.
1998,
Pubmed
,
Xenbase
Small,
Presenilins and the gamma-secretase: still a complex problem.
2010,
Pubmed
Sokolov,
Soluble amyloid oligomers increase bilayer conductance by altering dielectric structure.
2006,
Pubmed
Stutzmann,
Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability.
2004,
Pubmed
Taylor,
Pharmacological analysis of intracellular Ca2+ signalling: problems and pitfalls.
1998,
Pubmed
Tigyi,
A serum factor that activates the phosphatidylinositol phosphate signaling system in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Toescu,
Caffeine inhibits the agonist-evoked cytosolic Ca2+ signal in mouse pancreatic acinar cells by blocking inositol trisphosphate production.
1992,
Pubmed
Verkhratsky,
Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons.
2005,
Pubmed
Walsh,
Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo.
2002,
Pubmed
Wang,
beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology.
2000,
Pubmed
Yamasaki-Mann,
Enhanced ER Ca2+ store filling by overexpression of SERCA2b promotes IP3-evoked puffs.
2011,
Pubmed
,
Xenbase
Yao,
Quantal puffs of intracellular Ca2+ evoked by inositol trisphosphate in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Yao,
Inositol trisphosphate-mediated Ca2+ influx into Xenopus oocytes triggers Ca2+ liberation from intracellular stores.
1993,
Pubmed
,
Xenbase
van Meer,
Lipid map of the mammalian cell.
2011,
Pubmed
