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N-cadherin-based adhesion enhances Aβ release and decreases Aβ |
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| Authors: | Kengo Uemura Christina M Lill† Mary Banks† Megumi Asada‡ Nobuhisa Aoyagi Koichi Ando Masakazu Kubota‡ Takeshi Kihara§ Takaaki Nishimoto§ Hachiro Sugimoto§ Ryosuke Takahashi Bradley T Hyman† Shun Shimohama¶ Oksana Berezovska† Ayae Kinoshita‡ |
| Institution: | Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Alzheimer Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA; School of Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Department of Neurology, Sapporo Medical University, Sapporo, Japan |
| Abstract: | In neurons, Presenilin 1(PS1)/γ-secretase is located at the synapses, bound to N-cadherin. We have previously reported that N-cadherin-mediated cell–cell contact promotes cell-surface expression of PS1/γ-secretase. We postulated that N-cadherin-mediated trafficking of PS1 might impact synaptic PS1-amyloid precursor protein interactions and Aβ generation. In the present report, we evaluate the effect of N-cadherin-based contacts on Aβ production. We demonstrate that stable expression of N-cadherin in Chinese hamster ovary cells, expressing the Swedish mutant of human amyloid precursor protein leads to enhanced secretion of Aβ in the medium. Moreover, N-cadherin expression decreased Aβ |
| Keywords: | Alzheimer's disease amyloid β N-cadherin presenilin 1 synapse |