Effects of the amyloid protein precursor of Alzheimer's disease and other ligands of the LDL receptor-related protein on neurite outgrowth from sympathetic neurons in culture

Ronald B. Postuma, Ralph N. Martins, Roberto Cappai, Konrad Beyreuther, Colin L. Masters, Dudley K. Strickland, Su San Mok, David H. Small*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The amyloid protein precursor (APP) of Alzheimer's disease can stimulate neurite outgrowth in vitro. The receptor responsible for this effect has not been identified. Kunitz protease inhibitor (KPI)-containing forms of APP bind to the low-density lipoprotein receptor-related protein (LRP). As LRP may regulate neurite outgrowth, we examined whether the effects of APP are mediated by LRP. Inhibitors of LRP decreased neurite outgrowth from chick sympathetic neurons. Most LRP ligands (α-macroglobulin, lactoferrin, and lipoprotein lipase) stimulated outgrowth. However, in soluble form, the KPI- containing APP751 was a weak inhibitor of outgrowth. In substrate-bound form, both APP751 and APP695 (which does not bind to LRP) stimulated outgrowth. Thus the effect of substrate-bound APP on neurite outgrowth is not mediated by LRP.

Original languageEnglish
Pages (from-to)13-16
Number of pages4
JournalFEBS Letters
Volume428
Issue number1-2
DOIs
Publication statusPublished - 22 May 1998
Externally publishedYes

Keywords

  • Alzheimer
  • Amyloid protein precursor
  • Apolipoprotein E
  • Heparin
  • Low- density lipoprotein receptor-related protein

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