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A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death
The p75 neurotrophin receptor (p75(NTR)) is a known mediator of β-amyloid (Aβ)-induced neurotoxicity implicated in Alzheimer's disease (AD). Here, we demonstrate that death receptor 6 (DR6) binds to p75(NTR) and is a component of the p75(NTR) signaling complex responsible for Aβ-induced cortica...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641333/ https://www.ncbi.nlm.nih.gov/pubmed/23559013 http://dx.doi.org/10.1038/cddis.2013.110 |
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author | Hu, Y Lee, X Shao, Z Apicco, D Huang, G Gong, B J Pepinsky, R B Mi, S |
author_facet | Hu, Y Lee, X Shao, Z Apicco, D Huang, G Gong, B J Pepinsky, R B Mi, S |
author_sort | Hu, Y |
collection | PubMed |
description | The p75 neurotrophin receptor (p75(NTR)) is a known mediator of β-amyloid (Aβ)-induced neurotoxicity implicated in Alzheimer's disease (AD). Here, we demonstrate that death receptor 6 (DR6) binds to p75(NTR) and is a component of the p75(NTR) signaling complex responsible for Aβ-induced cortical neuron death. Cortical neurons isolated from either DR6 or p75(NTR) null mice are resistant to Aβ-induced neurotoxicity. Blocking DR6 function in cortical neurons by anti-DR6 antibodies that block the binding of DR6 to p75(NTR) receptor complex or by a dominant negative DR6 construct lacking the cytoplasmic signaling death domain attenuates Aβ-induced caspase 3 activation and cell death. DR6 expression is upregulated in AD cortex and correlates with elevated neuronal death. Targeting the disruption of the DR6/p75(NTR) complex to prevent Aβ cytotoxicity represents a new approach for the treatment of neurodegenerative disorders such as AD. |
format | Online Article Text |
id | pubmed-3641333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-36413332013-05-02 A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death Hu, Y Lee, X Shao, Z Apicco, D Huang, G Gong, B J Pepinsky, R B Mi, S Cell Death Dis Original Article The p75 neurotrophin receptor (p75(NTR)) is a known mediator of β-amyloid (Aβ)-induced neurotoxicity implicated in Alzheimer's disease (AD). Here, we demonstrate that death receptor 6 (DR6) binds to p75(NTR) and is a component of the p75(NTR) signaling complex responsible for Aβ-induced cortical neuron death. Cortical neurons isolated from either DR6 or p75(NTR) null mice are resistant to Aβ-induced neurotoxicity. Blocking DR6 function in cortical neurons by anti-DR6 antibodies that block the binding of DR6 to p75(NTR) receptor complex or by a dominant negative DR6 construct lacking the cytoplasmic signaling death domain attenuates Aβ-induced caspase 3 activation and cell death. DR6 expression is upregulated in AD cortex and correlates with elevated neuronal death. Targeting the disruption of the DR6/p75(NTR) complex to prevent Aβ cytotoxicity represents a new approach for the treatment of neurodegenerative disorders such as AD. Nature Publishing Group 2013-04 2013-04-04 /pmc/articles/PMC3641333/ /pubmed/23559013 http://dx.doi.org/10.1038/cddis.2013.110 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Original Article Hu, Y Lee, X Shao, Z Apicco, D Huang, G Gong, B J Pepinsky, R B Mi, S A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death |
title | A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death |
title_full | A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death |
title_fullStr | A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death |
title_full_unstemmed | A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death |
title_short | A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death |
title_sort | dr6/p75(ntr) complex is responsible for β-amyloid-induced cortical neuron death |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641333/ https://www.ncbi.nlm.nih.gov/pubmed/23559013 http://dx.doi.org/10.1038/cddis.2013.110 |
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