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

Khalil Saadipour, Noralyn Manucat-Tan, Yoon Lim, Damien Keating, Kevin Smith, Jin-Hua Zhong, Hong Liao, Larisa Bobrovskaya, Yan-Jiang Wang, Moses Chao, Xin-Fu Zhou

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    12 Citations (Scopus)

    Abstract

    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. (Figure presented.). Cover Image for this Issue: doi. 10.1111/jnc.14163.

    Original languageEnglish
    Pages (from-to)302-317
    Number of pages16
    JournalJournal of Neurochemistry
    Volume144
    Issue number3
    DOIs
    Publication statusPublished - 2018

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  • Cite this

    Saadipour, K., Manucat-Tan, N., Lim, Y., Keating, D., Smith, K., Zhong, J-H., Liao, H., Bobrovskaya, L., Wang, Y-J., Chao, M., & Zhou, X-F. (2018). p75 neurotrophin receptor interacts with and promotes BACE1 localization in endosomes aggravating amyloidogenesis. Journal of Neurochemistry, 144(3), 302-317. https://doi.org/10.1111/jnc.14206