Soluble β-amyloid Precursor Protein Alpha binds to p75 neurotrophin receptor to promote neurite outgrowth

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 o...

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Bibliographic Details
Published in:PloS one 2013-12, Vol.8 (12), p.e82321
Main Authors: Hasebe, Noriko, Fujita, Yuki, Ueno, Masaki, Yoshimura, Kazuhiro, Fujino, Yuji, Yamashita, Toshihide
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid beta-Protein Precursor - metabolism
Amyloid precursor protein
Anesthesiology
Animals
Axonogenesis
Binding sites
Brain research
Cercopithecus aethiops
Cerebral Cortex - metabolism
COS Cells
Critical care
Enzyme-linked immunosorbent assay
Fragments
Growth factors
Kinases
Laboratory animals
Medicine
Mice
Neurites - metabolism
Neurons - metabolism
Neurosciences
Neurotoxicity
Peptides
Precursors
Proteins
R&D
Receptor, Nerve Growth Factor - metabolism
Research & development
Rodents
Science
β-Amyloid
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Summary: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. 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). We conclude that p75(NTR) is the receptor for sAPPα to mediate neurotrophic effects.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0082321