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p75 neurotrophin receptor interacts with and promotes BACE1 localization in endosomes aggravating amyloidogenesis.

Journal of neurochemistry | 2018

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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Streptavidin antibody (HRP) (antibody)

RRID:AB_1288825

This polyclonal targets Streptavidin antibody (HRP)

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Phospho-BACE1 (Ser498) Polyclonal Antibody (antibody)

RRID:AB_10989983

This polyclonal targets Phospho-BACE1 (Ser498)

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HA tag antibody (antibody)

RRID:AB_10637297

This polyclonal targets HA tag antibody

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EEA1 (antibody)

RRID:AB_10703311

This monoclonal targets EEA1

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HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Ngfrtm1Gdc/Ngfrtm1Gdc (organism)

RRID:MGI:2450868

Allele Detail: Targeted This is a legacy resource.

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