| First Author | Hasebe N | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e82321 |
| PubMed ID | 24358169 | Mgi Jnum | J:211143 |
| Mgi Id | MGI:5574151 | Doi | 10.1371/journal.pone.0082321 |
| Citation | Hasebe N, et al. (2013) Soluble beta-amyloid Precursor Protein Alpha binds to p75 neurotrophin receptor to promote neurite outgrowth. PLoS One 8(12):e82321 |
| abstractText | BACKGROUND: The cleavage of beta-amyloid precursor protein (APP) generates multiple proteins: Soluble beta-amyloid Precursor Protein Alpha (sAPPalpha), sAPPbeta, and amyloid beta (Abeta). Previous studies have shown that sAPPalpha and sAPPbeta possess neurotrophic properties, whereas Abeta 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 sAPPalpha-mediated neurotrophic effects. sAPPalpha and sAPPbeta interact with p75 neurotrophin receptor (p75(NTR)), and sAPPalpha promotes neurite outgrowth. METHODS AND FINDINGS: First, we investigated whether APP fragments interact with p75(NTR), because full-length APP and Abeta have been shown to interact with p75(NTR) in vitro. Both sAPPalpha and sAPPbeta were co-immunoprecipitated with p75(NTR) and co-localized with p75(NTR) on COS-7 cells. The binding affinity of sAPPalpha and sAPPbeta for p75(NTR) was confirmed by enzyme-linked immunosorbent assay (ELISA). Next, we investigated the effect of sAPPalpha on neurite outgrowth in mouse cortical neurons. Neurite outgrowth was promoted by sAPPalpha, but sAPPalpha was uneffective in a knockdown of p75(NTR). CONCLUSION: We conclude that p75(NTR) is the receptor for sAPPalpha to mediate neurotrophic effects. |
