Interaction between amyloid precursor protein and Nogo receptors regulates amyloid deposition

Xiang Dong Zhou, Xiang You Hu, Wan Xia He, Xiao Ying Tang, Shi Qi, Zhuohua Zhang, Ri Qiang Yan

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Excessive production or accumulation of β-amyloid (Aβ) peptides in human brains leads to increased amyloid deposition and cognitive dysfunction, which are invariable pathological features in patients with Alzheimer's disease (AD). Many cellular factors can regulate the production of Aβ. In this study, we show that a family of proteins named Nogo receptor proteins (NgR1 to NgR3) regulates Aβ production via interaction with amyloid precursor protein (APP). Further mapping of the interacting domain indicates that a small region adjacent to the BACE1 cleavage site of APP mediates interaction of APP with Nogo receptor proteins. Our results also indicate that increased interaction between Nogo receptor and APP reduces surface expression of APP and favors processing of APP by BACE1. When NgR2 was ablated in AD transgenic mice expressing Swedish APP and PS1ΔE9, amyloid deposition was clearly reduced (0.66% of total measured area in APP swe/PS1ΔE9/NgR2 -/- mice vs. 0.76% of total measured area in APP swe/ PS1ΔE9 mice). Our results demonstrate that down-regulation of NgR expression is a potential approach for inhibiting amyloid deposition in AD patients.

    Original languageEnglish
    Pages (from-to)3146-3156
    Number of pages11
    JournalFASEB Journal
    Volume25
    Issue number9
    DOIs
    Publication statusPublished - Sep 2011

    Keywords

    • Alzheimer's disease
    • BACE1
    • Reticulon

    Fingerprint Dive into the research topics of 'Interaction between amyloid precursor protein and Nogo receptors regulates amyloid deposition'. Together they form a unique fingerprint.

  • Cite this

    Zhou, X. D., Hu, X. Y., He, W. X., Tang, X. Y., Qi, S., Zhang, Z., & Yan, R. Q. (2011). Interaction between amyloid precursor protein and Nogo receptors regulates amyloid deposition. FASEB Journal, 25(9), 3146-3156. https://doi.org/10.1096/fj.11-184325