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Shuttling protein nucleolin is a microglia receptor for amyloid beta peptide 1-42

Daisuke Ozawa1, Takashi Nakamura, Masanori Koike

  • 1School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.

Biological & Pharmaceutical Bulletin
|August 6, 2013
PubMed

Insights

Nucleolin acts as a scavenger receptor, enabling microglia to recognize and clear amyloid-beta 42 (Aβ42) peptides, crucial for Alzheimer's disease neurotoxicity. This interaction facilitates Aβ42 phagocytosis by brain immune cells.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) is characterized by neurotoxicity linked to amyloid-beta 42 (Aβ42) peptides.
  • Microglia, the brain's mononuclear phagocytes, possess the capacity to clear Aβ through phagocytosis.
  • Nucleolin, a shuttling protein, has recently demonstrated scavenger receptor activity.

Purpose of the Study:

  • To determine if nucleolin specifically interacts with Aβ42.
  • To investigate if nucleolin mediates Aβ42 phagocytosis by microglia.

Main Methods:

  • Surface plasmon resonance (SPR) to assess nucleolin-Aβ binding.
  • Immunofluorescence staining to detect cell surface nucleolin expression.
  • Phagocytosis assays using microglial cells and nucleolin-transfected cells, with and without Aβ40/Aβ42 and anti-nucleolin antibody or aptamer (AGRO).

Main Results:

  • Microglial cells phagocytosed monomeric and fibril Aβ42 more effectively than Aβ40.
  • SPR confirmed strong nucleolin association with Aβ42 and weak association with Aβ40.
  • Cell surface nucleolin was detected on microglia; blocking nucleolin inhibited Aβ42 phagocytosis.
  • Nucleolin-transfected cells showed Aβ42 phagocytosis but not Aβ40 phagocytosis.
  • The nucleolin-specific aptamer AGRO inhibited Aβ42 phagocytosis but not Aβ40 phagocytosis.

Conclusions:

  • Nucleolin functions as a specific receptor for Aβ42.
  • This receptor-mediated recognition by nucleolin facilitates microglial phagocytosis of Aβ42.
  • Targeting the nucleolin-Aβ42 interaction may offer therapeutic strategies for Alzheimer's disease.

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