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A DR6/p75(NTR) complex is responsible for β-amyloid-induced cortical neuron death.
- Source :
-
Cell death & disease [Cell Death Dis] 2013 Apr 04; Vol. 4, pp. e579. Date of Electronic Publication: 2013 Apr 04. - Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- 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
Cerebral Cortex drug effects
Neurons drug effects
Receptors, Nerve Growth Factor genetics
Receptors, Tumor Necrosis Factor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 23559013
- Full Text :
- https://doi.org/10.1038/cddis.2013.110