GM1 inhibits amyloid β-protein-induced cytokine release

Toshio Ariga, Robert K Yu

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The ganglioside GM1 is known to play a pivotal role in neuronal survival and/or regeneration. Recently it has been shown that GM1 binds tightly with membrane-bound amyloid β protein (Aβ) and prevents its conversion from a helical to a β-sheet structure. To examine the potential physiological consequences of this binding, we studied the effect of GM1 on Aβ-stimulated release of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6 and TNF-α, using the human monocytic cell line, THP-1, as a model system. Treatment of THP-1 cells with Aβ 1-40 or Aβ 2535 resulted in an increased cytokine release from these cells. However, treatment of Aβ-activated THP-1 cells with GM1 and several other complex gangliosides, but not hematosides and neutral glycosphingolipids such as asialo-GM1 (GA1), lactosylceramide, and globoside, significantly decreased the cytokine release. In contrast, this effect was not observed for lipopolysaccharide (LPS)activated and thrombin-activated THP-1 cells, indicating that the ganglioside effect is specific for Aβ-induced cytokine release. A direct interaction between GM1 and Aβ was demonstrated using the surface plasmon resonance technique. We found that GM1 ganglioside exhibited higher affinity for Aβ 1-40 than GA1, suggesting that the sialic acid moiety of GM1 is necessary for its interaction with Aβ. We conclude that the inhibitory effect of GM1 on Aβ- induced cytokine release may reflect pre-existing abnormalities in membrane transport at the stage of amyloid formation and that GM1 may induce conformational changes in Aβ, resulting in diminished fibrillogenesis and prevention of the inflammatory response of neuronal cells in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)219-226
Number of pages8
JournalNeurochemical Research
Volume24
Issue number2
DOIs
StatePublished - Feb 13 1999
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid β-protein
  • Cytokines
  • GM1 ganglioside
  • Interleukin-1 β, interleukin-6
  • Tumor necrosis factor- α

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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