Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment.
The p75 neurotrophin receptor (p75(NTR)) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75(NTR) ligands found to promote survival signaling might prevent Abeta-induced degeneration and synaptic dysfunction....
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003604&type=printable |
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| author | Tao Yang Juliet K Knowles Qun Lu Hong Zhang Ottavio Arancio Laura A Moore Timothy Chang Qian Wang Katrin Andreasson Jayakumar Rajadas Gerald G Fuller Youmei Xie Stephen M Massa Frank M Longo |
| author_facet | Tao Yang Juliet K Knowles Qun Lu Hong Zhang Ottavio Arancio Laura A Moore Timothy Chang Qian Wang Katrin Andreasson Jayakumar Rajadas Gerald G Fuller Youmei Xie Stephen M Massa Frank M Longo |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | The p75 neurotrophin receptor (p75(NTR)) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75(NTR) ligands found to promote survival signaling might prevent Abeta-induced degeneration and synaptic dysfunction. These ligands inhibited Abeta-induced neuritic dystrophy, death of cultured neurons and Abeta-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Abeta-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3beta and c-Jun, and tau phosphorylation, and prevented Abeta-induced inactivation of AKT and CREB. Finally, a p75(NTR) ligand blocked Abeta-induced hippocampal LTP impairment. These studies support an extensive intersection between p75(NTR) signaling and Abeta 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 Abeta-induced neuronal dystrophy and death. |
| format | Article |
| id | doaj-art-94a2899ce30f40dcafdb4ae05c1625d0 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-94a2899ce30f40dcafdb4ae05c1625d02025-08-20T02:00:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01311e360410.1371/journal.pone.0003604Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment.Tao YangJuliet K KnowlesQun LuHong ZhangOttavio ArancioLaura A MooreTimothy ChangQian WangKatrin AndreassonJayakumar RajadasGerald G FullerYoumei XieStephen M MassaFrank M LongoThe p75 neurotrophin receptor (p75(NTR)) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75(NTR) ligands found to promote survival signaling might prevent Abeta-induced degeneration and synaptic dysfunction. These ligands inhibited Abeta-induced neuritic dystrophy, death of cultured neurons and Abeta-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited Abeta-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3beta and c-Jun, and tau phosphorylation, and prevented Abeta-induced inactivation of AKT and CREB. Finally, a p75(NTR) ligand blocked Abeta-induced hippocampal LTP impairment. These studies support an extensive intersection between p75(NTR) signaling and Abeta 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 Abeta-induced neuronal dystrophy and death.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003604&type=printable |
| spellingShingle | Tao Yang Juliet K Knowles Qun Lu Hong Zhang Ottavio Arancio Laura A Moore Timothy Chang Qian Wang Katrin Andreasson Jayakumar Rajadas Gerald G Fuller Youmei Xie Stephen M Massa Frank M Longo Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. PLoS ONE |
| title | Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. |
| title_full | Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. |
| title_fullStr | Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. |
| title_full_unstemmed | Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. |
| title_short | Small molecule, non-peptide p75 ligands inhibit Abeta-induced neurodegeneration and synaptic impairment. |
| title_sort | small molecule non peptide p75 ligands inhibit abeta induced neurodegeneration and synaptic impairment |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003604&type=printable |
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