| First Author | Hu Y | Year | 2013 |
| Journal | Cell Death Dis | Volume | 4 |
| Pages | e579 | PubMed ID | 23559013 |
| Mgi Jnum | J:205745 | Mgi Id | MGI:5546316 |
| Doi | 10.1038/cddis.2013.110 | Citation | Hu Y, et al. (2013) A DR6/p75(NTR) complex is responsible for beta-amyloid-induced cortical neuron death. Cell Death Dis 4:e579 |
| abstractText | The p75 neurotrophin receptor (p75(NTR)) is a known mediator of beta-amyloid (Abeta)-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 Abeta-induced cortical neuron death. Cortical neurons isolated from either DR6 or p75(NTR) null mice are resistant to Abeta-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 Abeta-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 Abeta cytotoxicity represents a new approach for the treatment of neurodegenerative disorders such as AD. |
