Activation of protein kinase C modulates BACE1-mediated β-secretase activity

Lizhen Wang, Hoon Shim, Chengsong Xie, Huaibin Cai

    Research output: Contribution to journalArticle

    Abstract

    β-Site APP cleavage enzyme 1 (BACE1) is the β-secretase responsible for generating amyloid-β (Aβ) peptides in Alzheimer's disease (AD). Previous studies suggest that activation of protein kinase C (PKC) modulates the β-secretase-mediated cleavage of APP and reduces the production of Aβ. The mechanism of PKC-mediated modulation of β-secretase activity, however, remains elusive. We report here that activation of PKC modulated β-secretase activity through either suppressing the accumulation or promoting the translocation of BACE1 protein in a cell type-dependent manner. We found that activation of PKC suppressed the accumulation of BACE1 protein in fibroblasts through an enhancement of intracellular protease activities. In neurons, activation of PKC did not alter the expression level of BACE1, but led to more BACE1 translocated to the cell surface, resulting in a decreased cleavage of APP at the β1 site. Together, Our findings provide novel mechanisms of PKC-mediated modulation of β-secretase activity, suggesting that alteration of the intracellular trafficking of BACE1 may serve as a useful therapeutic strategy to lower the production of Aβ in AD.

    Original languageEnglish (US)
    Pages (from-to)357-367
    Number of pages11
    JournalNeurobiology of Aging
    Volume29
    Issue number3
    DOIs
    StatePublished - Mar 1 2008

    Keywords

    • APP
    • Amyloid β
    • BACE1
    • Fibroblast
    • Neuron
    • PKC
    • Protein degradation
    • Protein translocation
    • β-Secretase

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Aging
    • Clinical Neurology
    • Developmental Biology
    • Geriatrics and Gerontology

    Fingerprint Dive into the research topics of 'Activation of protein kinase C modulates BACE1-mediated β-secretase activity'. Together they form a unique fingerprint.

  • Cite this