Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers
- PMID: 17192927
- DOI: 10.1002/ana.21051
Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers
Abstract
Objective: Despite progress in defining a pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, orally bioavailable compounds that prevent its effects on hippocampal synaptic plasticity and cognitive function have not yet emerged. A particularly attractive therapeutic strategy is to selectively neutralize small, soluble Abeta oligomers that have recently been shown to mediate synaptic dysfunction.
Methods: Using electrophysiological, biochemical, and behavioral assays, we studied how scyllo-inositol (AZD-103; molecular weight, 180) neutralizes the acutely toxic effects of Abeta on synaptic function and memory recall.
Results: Scyllo-inositol, but not its stereoisomer, chiro-inositol, dose-dependently rescued long-term potentiation in mouse hippocampus from the inhibitory effects of soluble oligomers of cell-derived human Abeta. Cerebroventricular injection into rats of the soluble Abeta oligomers interfered with learned performance on a complex lever-pressing task, but administration of scyllo-inositol via the drinking water fully prevented oligomer-induced errors.
Interpretation: A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble Abeta oligomers through a mechanism that restores hippocampal synaptic plasticity.
Similar articles
-
Arginine vasopressin prevents amyloid beta protein-induced impairment of long-term potentiation in rat hippocampus in vivo.Neurosci Lett. 2009 Feb 6;450(3):306-10. doi: 10.1016/j.neulet.2008.11.053. Epub 2008 Nov 28. Neurosci Lett. 2009. PMID: 19059464
-
Imipramine, in part through tumor necrosis factor alpha inhibition, prevents cognitive decline and beta-amyloid accumulation in a mouse model of Alzheimer's disease.J Pharmacol Exp Ther. 2010 Feb;332(2):505-14. doi: 10.1124/jpet.109.162164. Epub 2009 Nov 4. J Pharmacol Exp Ther. 2010. PMID: 19889791
-
Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress.Brain Res. 2010 Apr 30;1328:152-61. doi: 10.1016/j.brainres.2010.02.046. Epub 2010 Feb 19. Brain Res. 2010. PMID: 20171955
-
Synaptic plasticity disruption by amyloid beta protein: modulation by potential Alzheimer's disease modifying therapies.Biochem Soc Trans. 2005 Aug;33(Pt 4):563-7. doi: 10.1042/BST0330563. Biochem Soc Trans. 2005. PMID: 16042545 Review.
-
The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention.Biochem Soc Trans. 2005 Nov;33(Pt 5):1087-90. doi: 10.1042/BST20051087. Biochem Soc Trans. 2005. PMID: 16246051 Review.
Cited by
-
Aβ42-binding peptoids as amyloid aggregation inhibitors and detection ligands.ACS Chem Neurosci. 2013 Jun 19;4(6):952-62. doi: 10.1021/cn400011f. Epub 2013 Mar 7. ACS Chem Neurosci. 2013. PMID: 23427915 Free PMC article.
-
Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer's disease immunotherapeutics.Alzheimers Res Ther. 2014 Jul 9;6(4):42. doi: 10.1186/alzrt272. eCollection 2014. Alzheimers Res Ther. 2014. PMID: 25045405 Free PMC article. Review.
-
Use of copper and insulin-resistance to accelerate cognitive deficits and synaptic protein loss in a rat Abeta-infusion Alzheimer's disease model.J Alzheimers Dis. 2008 Dec;15(4):625-40. doi: 10.3233/jad-2008-15409. J Alzheimers Dis. 2008. PMID: 19096161 Free PMC article.
-
Cerebrovascular lesions induce transient β-amyloid deposition.Brain. 2011 Dec;134(Pt 12):3697-707. doi: 10.1093/brain/awr300. Epub 2011 Nov 26. Brain. 2011. PMID: 22120142 Free PMC article.
-
Systematic analysis of time-dependent neural effects of soluble amyloid β oligomers in culture and in vivo: Prevention by scyllo-inositol.Neurobiol Dis. 2015 Oct;82:152-163. doi: 10.1016/j.nbd.2015.05.020. Epub 2015 Jun 6. Neurobiol Dis. 2015. PMID: 26054438 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical