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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Y, Lee, X, Shao, Z, Apicco, D, Huang, G, Gong, B J, Pepinsky, R B, Mi, S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
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
_version_ 1782268003570679808
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
work_keys_str_mv AT huy adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT leex adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT shaoz adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT apiccod adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT huangg adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT gongbj adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT pepinskyrb adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT mis adr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT huy dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT leex dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT shaoz dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT apiccod dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT huangg dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT gongbj dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT pepinskyrb dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath
AT mis dr6p75ntrcomplexisresponsibleforbamyloidinducedcorticalneurondeath