Different Conformations of Amyloid Beta Induce Neurotoxicity by Distinct Mechanisms in Human Cortical Neurons.
From: Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: May 2006
- ISSN: 1529-2401
- Volume: 26
- Issue: 22
- Pages: 6011-8
- Medium: Internet
- Language: English
- Citation (JAMA): Deshpande Atul, Mina Erene, Glabe Charles, et al. Different Conformations of Amyloid Beta Induce Neurotoxicity by Distinct Mechanisms in Human Cortical Neurons.. J. Neurosci. May 2006;26:6011-8
Abstract
Characterization of soluble oligomeric amyloid beta (Abeta) species in the brains of Alzheimer’s disease (AD) patients and transgenic models has raised the possibility that different conformations of Abeta may contribute to AD pathology via different mechanisms. To characterize the toxic effect of different Abeta conformations, we tested side by side the effect of well characterized Abeta oligomers (AbetaOs), Abeta-derived diffusible ligands (ADDLs), and fibrillar Abeta (Abetaf) preparations in human cortical neurons (HCNs). Both AbetaOs and ADDLs bind rapidly and with high affinity to synaptic contacts and cellular membranes. AbetaOs (5 microm) induced rapid and massive neuronal death. Calcium influx accelerated, but was not required for, AbetaO toxicity. AbetaOs elicited a stereotyped succession of cellular changes consistent with the activation of a mitochondrial death apoptotic pathway. At low concentrations AbetaOs caused chronic and subtler mitochondrial alterations but minimal cell death. ADDLs induced similar toxic changes as AbetaOs but on a fivefold longer time scale. Higher concentrations of Abetaf and longer incubation times were required to produce widespread neuritic dystrophy but modest HCN cell death. Thus various Abeta species may play relevant roles in AD, causing neurotoxicity by distinct non-overlapping mechanisms affecting neuronal function and viability over multiple time courses.
Mesh Headings (Keywords): Alzheimer Disease, Amyloid beta-Protein, Apoptosis, Cells, Cultured, Cerebral Cortex, Humans, Neurons, Neurotoxins, Protein Conformation, Synapses
Check for Full Text / PubMed Unique Identifier (PMID): 16738244
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.