Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deposition of amyloid beta (Aβ) and dysregulation of neurotrophic signaling, causing synaptic dysfunction, loss of memory, and cell death. The expression of p75 neurotrophin receptor is elevated in the brain of AD patients, suggesting its involvement in this disease. However, the exact mechanism of its action is not yet clear. Here, we show that p75 interacts with beta-site amyloid precursor protein cleaving enzyme-1 (BACE1), and this interaction is enhanced in the presence of Aβ. Our results suggest that the colocalization of BACE1 and amyloid precursor protein (APP) is increased in the presence of both Aβ and p75 in cortical neurons. In addition, the localization of APP and BACE1 in early endosomes is increased in the presence of Aβ and p75. An increased phosphorylation of APP-Thr668 and BACE1-Ser498 by c-Jun N-terminal kinase (JNK) in the presence of Aβ and p75 could be responsible for this localization. In conclusion, our study proposes a potential involvement in amyloidogenesis for p75, which may represent a future therapeutic target for AD. Cover Image for this Issue: doi. 10.1111/jnc.14163.
Pubmed ID: 28869759 RIS Download
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This polyclonal secondary targets IgM
View all literature mentionsThis isotype control targets Not Applicable
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets Streptavidin antibody (HRP)
View all literature mentionsThis polyclonal targets Phospho-BACE1 (Ser498)
View all literature mentionsThis polyclonal targets Human APP, phospho (Thr668)
View all literature mentionsThis polyclonal targets HA tag antibody
View all literature mentionsThis unknown targets GFP Antibody
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Human BACE-1
View all literature mentionsThis polyclonal targets Human p75
View all literature mentionsThis monoclonal targets APP (Amyloid Precursor Protein)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
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