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Author | Yang, Tao | en_US |
Author | Knowles, Juliet K. | en_US |
Author | Lu, Qun | en_US |
Author | Zhang, Hong | en_US |
Author | Arancio, Ottavio | en_US |
Author | Moore, Laura A. | en_US |
Author | Chang, Timothy | en_US |
Author | Wang, Qian | en_US |
Author | Andreasson, Katrin | en_US |
Author | Rajadas, Jayakumar | en_US |
Author | Fuller, Gerald G. | en_US |
Author | Xie, Youmei | en_US |
Author | Massa, Stephen M. | en_US |
Author | Longo, Frank M. | en_US |
Date Accessioned | 2011-04-28T19:22:36Z | en_US |
Date Accessioned | 2011-05-17T13:03:53Z | |
Date Available | 2011-04-28T19:22:36Z | en_US |
Date Available | 2011-05-17T13:03:53Z | |
Date of Issue | 2008-11-03 | en_US |
Identifier (Citation) | PLoS ONE; 3:11 p. e3604 | en_US |
Identifier (URI) | http://hdl.handle.net/10342/3430 | en_US |
Description | The p75 neurotrophin receptor (p75NTR) is expressed by neurons particularly vulnerable in Alzheimer’s disease (AD). We tested the hypothesis that non-peptide, small molecule p75NTR ligands found to promote survival signaling might prevent Abinduced degeneration and synaptic dysfunction. These ligands inhibited Ab-induced neuritic dystrophy, death of cultured neurons and Ab-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Ab-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3b and c-Jun, and tau phosphorylation, and prevented Ab-induced inactivation of AKT and CREB. Finally, a p75NTR ligand blocked Ab-induced hippocampal LTP impairment. These studies support an extensive intersection between p75NTR signaling and Ab pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Ab-induced neuronal dystrophy and death. Originally published PLoS ONE, Vol. 3, No. 11, Nov 2008 | en_US |
Language | en_US | en_US |
Publisher | East Carolina University | en_US |
Related URI | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003604 | en_US |
Rights | Author notified of opt-out rights by Cammie Jennings prior to upload of this article. | en_US |
Subject | Alzheimer's disease | en_US |
Subject | P75 neurotrophin receptor | en_US |
Subject | Small molecule ligands | en_US |
Title | Small Molecule, Non-Peptide p75NTR Ligands Inhibit Aß-Induced Neurodegeneration and Synaptic Impairment | en_US |
Type | Article | en_US |
Identifier (PMID) | PMC2575383 | en_US |