Chloroquine-induced endocytic pathway abnormalities: Cellular model of GM1 ganglioside-induced Abeta fibrillogenesis in Alzheimer's disease

FEBS Lett. 2006 Dec 22;580(30):6972-6. doi: 10.1016/j.febslet.2006.11.072. Epub 2006 Dec 5.

Abstract

Endocytic pathway abnormalities were previously observed in brains affected with Alzheimer's disease (AD). To clarify the pathological relevance of these abnormalities to assembly of amyloid beta-protein (Abeta), we treated PC12 cells with chloroquine, which potently perturbs membrane trafficking from endosomes to lysosomes. Chloroquine treatment induced accumulation of GM1 ganglioside (GM1) in Rab5-positive enlarged early endosomes and on the cell surface. Notably, an increase in GM1 level on the cell surface was sufficient to induce Abeta assembly. Our results suggest that endocytic pathway abnormalities in AD brain induce GM1 accumulation on the cell surface, leading to amyloid fibril formation in brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid / chemistry*
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Chloroquine / pharmacology*
  • Endocytosis / drug effects*
  • Endosomes / drug effects
  • Endosomes / metabolism
  • G(M1) Ganglioside / metabolism*
  • PC12 Cells
  • Protein Binding
  • Rats
  • Time Factors
  • rab5 GTP-Binding Proteins / metabolism

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • G(M1) Ganglioside
  • Chloroquine
  • rab5 GTP-Binding Proteins