| First Author | Xu Y | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 1 | Pages | 157-68 |
| PubMed ID | 25150572 | Mgi Jnum | J:218312 |
| Mgi Id | MGI:5617289 | Doi | 10.1016/j.neurobiolaging.2014.07.027 |
| Citation | Xu Y, et al. (2015) Beta amyloid-induced upregulation of death receptor 6 accelerates the toxic effect of N-terminal fragment of amyloid precursor protein. Neurobiol Aging 36(1):157-68 |
| abstractText | Amyloid precursor protein (APP) plays essential roles in the development of the Alzheimer's disease. Although full-length APP has been thoroughly studied, the role of the cleavage fragments especially the N-terminal fragments (N-APPs) in Alzheimer's disease pathogenesis was still elusive. In this study, we demonstrated that application of recombinant APP(1)(8)(-)(2)(8)(6) could enhance beta amyloid (Abeta)-induced neuronal injuries which were related to the activation of apoptosis proteins. Abeta treatment could induce a slight increase of N-APPs release. In addition, expression of death receptor 6 (DR6) was increased in Abeta-treated neurons and APP transgenic mice. Moreover, the effect of APP(1)(8)(-)(2)(8)(6) on Abeta-induced injuries could be suppressed by the application of recombinant DR6(4)(1)(-)(3)(4)(1) and DR6 antibody. Furthermore, pull-down assay revealed that APP(1)(8)(-)(2)(8)(6) could bind both exogenous and endogenous DR6. Abeta promoted APP(1)(8)(-)(2)(8)(6) targeting to neuron which was accompanied with the increase of DR6 expression, whereas downregulation of DR6 by interference RNA could alleviate the binding of N-APPs to neuron and also suppressed Abeta-dependent toxic effect with N-APPs. These results suggested that APP N-terminal fragments might play neurotoxic roles in Abeta-induced neuronal injuries through cell surface DR6. |
