title: Soluble β-amyloid Precursor Protein Alpha binds to p75 neurotrophin receptor to promote neurite outgrowth.
abstract: BACKGROUND
  The cleavage of β-amyloid precursor protein (APP) generates multiple proteins: Soluble β-amyloid Precursor Protein Alpha (sAPPα), sAPPβ, and amyloid β (Aβ). Previous studies have shown that sAPPα and sAPPβ possess neurotrophic properties, whereas Aβ 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 sAPPα-mediated neurotrophic effects. sAPPα and sAPPβ interact with p75 neurotrophin receptor (p75(NTR)), and sAPPα promotes neurite outgrowth.
  
  
  RESULTS
  First, we investigated whether APP fragments interact with p75(NTR), because full-length APP and Aβ have been shown to interact with p75(NTR) in vitro. Both sAPPα and sAPPβ were co-immunoprecipitated with p75(NTR) and co-localized with p75(NTR) on COS-7 cells. The binding affinity of sAPPα and sAPPβ for p75(NTR) was confirmed by enzyme-linked immunosorbent assay (ELISA). Next, we investigated the effect of sAPPα on neurite outgrowth in mouse cortical neurons. Neurite outgrowth was promoted by sAPPα, but sAPPα was uneffective in a knockdown of p75(NTR).
  
  
  CONCLUSIONS
  We conclude that p75(NTR) is the receptor for sAPPα to mediate neurotrophic effects.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan ; Department of Anesthesiology and Critical Care Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan ; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hasebe
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan ; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan ; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan ; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan ; Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujino
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan ; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002540:Cerebral Cortex / Q000378:metabolism*; D002522:Chlorocebus aethiops; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D020800:Receptor, Nerve Growth Factor