%0 Journal Article
%T Soluble ¦Â-amyloid Precursor Protein Alpha Binds to p75 Neurotrophin Receptor to Promote Neurite Outgrowth
%A Noriko Hasebe
%A Yuki Fujita
%A Masaki Ueno
%A Kazuhiro Yoshimura
%A Yuji Fujino
%A Toshihide Yamashita
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0082321
%X Background The cleavage of ¦Â-amyloid precursor protein (APP) generates multiple proteins: Soluble ¦Â-amyloid Precursor Protein Alpha (sAPP¦Á), sAPP¦Â, and amyloid ¦Â (A¦Â). Previous studies have shown that sAPP¦Á and sAPP¦Â possess neurotrophic properties, whereas A¦Â is neurotoxic. However, the underlying mechanism of the opposing effects of APP fragments remains poorly understood. In this study, we have investigated the mechanism of sAPP¦Á-mediated neurotrophic effects. sAPP¦Á and sAPP¦Â interact with p75 neurotrophin receptor (p75NTR), and sAPP¦Á promotes neurite outgrowth. Methods and Findings First, we investigated whether APP fragments interact with p75NTR, because full-length APP and A¦Â have been shown to interact with p75NTR in vitro. Both sAPP¦Á and sAPP¦Â were co-immunoprecipitated with p75NTR and co-localized with p75NTR on COS-7 cells. The binding affinity of sAPP¦Á and sAPP¦Â for p75NTR was confirmed by enzyme-linked immunosorbent assay (ELISA). Next, we investigated the effect of sAPP¦Á on neurite outgrowth in mouse cortical neurons. Neurite outgrowth was promoted by sAPP¦Á, but sAPP¦Á was uneffective in a knockdown of p75NTR. Conclusion We conclude that p75NTR is the receptor for sAPP¦Á to mediate neurotrophic effects.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0082321