The 37kDa/67kDa laminin receptor acts as a receptor for Aβ42 internalization

Sci Rep. 2014 Jul 3;4:5556. doi: 10.1038/srep05556.

Abstract

Neuronal loss is a major neuropathological hallmark of Alzheimer's disease (AD). The associations between soluble Aβ oligomers and cellular components cause this neurotoxicity. The 37 kDa/67 kDa laminin receptor (LRP/LR) has recently been implicated in Aβ pathogenesis. In this study the mechanism underlying the pathological role of LRP/LR was elucidated. Försters Resonance Energy Transfer (FRET) revealed that LRP/LR and Aβ form a biologically relevant interaction. The ability of LRP/LR to form stable associations with endogenously shed Aβ was confirmed by pull down assays and Aβ-ELISAs. Antibody blockade of this association significantly lowered Aβ42 induced apoptosis. Furthermore, antibody blockade and shRNA mediated downregulation of LRP/LR significantly hampered Aβ42 internalization. These results suggest that LRP/LR is a receptor for Aβ42 internalization, mediating its endocytosis and contributing to the cytotoxicity of the neuropeptide by facilitating intra-cellular Aβ42 accumulation. These findings recommend anti-LRP/LR specific antibodies and shRNAs as potential therapeutic tools for AD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Apoptosis
  • Endocytosis
  • HEK293 Cells
  • Humans
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Protein Stability
  • Protein Transport
  • Receptors, Laminin / metabolism
  • Ribosomal Proteins

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • RPSA protein, human
  • Receptors, Laminin
  • Ribosomal Proteins
  • amyloid beta-protein (1-42)