A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death.

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Abstrakt

Tytuł:: A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death.
Autorzy:: Hu Y; Department of Discovery Neurobiology, BiogenIdec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA.
Lee X
Shao Z
Apicco D
Huang G
Gong BJ
Pepinsky RB
Mi S
Źródło:: Cell death & disease [Cell Death Dis] 2013 Apr 04; Vol. 4, pp. e579. Date of Electronic Publication: 2013 Apr 04.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: London : Nature Pub. Group
MeSH Terms:: Cerebral Cortex/*drug effects
Neurons/*drug effects
Receptors, Nerve Growth Factor/*genetics
Receptors, Tumor Necrosis Factor/*genetics
Amyloid beta-Peptides/pharmacology ; Animals ; Antibodies/pharmacology ; Caspase 3/genetics ; Caspase 3/metabolism ; Cell Death/drug effects ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Gene Expression Regulation/drug effects ; Mice ; Mice, Knockout ; Neurons/metabolism ; Neurons/pathology ; Primary Cell Culture ; Protein Binding ; Receptors, Nerve Growth Factor/deficiency ; Receptors, Tumor Necrosis Factor/deficiency ; Signal Transduction/drug effects
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Substance Nomenclature:: 0 (Amyloid beta-Peptides)
0 (Antibodies)
0 (Receptors, Nerve Growth Factor)
0 (Receptors, Tumor Necrosis Factor)
0 (Ngfr protein, mouse)
0 (Tnfrsf21 protein, mouse)
EC 3.4.22.- (Caspase 3)
Entry Date(s):: Date Created: 20130406 Date Completed: 20130823 Latest Revision: 20231213
Update Code:: 20240104
PubMed Central ID:: PMC3641333
DOI:: 10.1038/cddis.2013.110
PMID:: 23559013
: Czasopismo naukowe

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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.

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