Document Detail

GM1 inhibits amyloid beta-protein-induced cytokine release.
MedLine Citation:
PMID:  9972868     Owner:  NLM     Status:  MEDLINE    
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 beta protein (A beta) and prevents its conversion from a helical to a beta-sheet structure. To examine the potential physiological consequences of this binding, we studied the effect of GM1 on A beta-stimulated release of proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and TNF-alpha, using the human monocytic cell line, THP-1, as a model system. Treatment of THP-1 cells with A beta 1-40 or A beta 25-35 resulted in an increased cytokine release from these cells. However, treatment of A beta-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 A beta-induced cytokine release. A direct interaction between GM1 and A beta was demonstrated using the surface plasmon resonance technique. We found that GM1 ganglioside exhibited higher affinity for A beta 1-40 than GA1, suggesting that the sialic acid moiety of GM1 is necessary for its interaction with A beta. We conclude that the inhibitory effect of GM1 on A beta-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 A beta, resulting in diminished fibrillogenesis and prevention of the inflammatory response of neuronal cells in Alzheimer's disease.
T Ariga; R K Yu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neurochemical research     Volume:  24     ISSN:  0364-3190     ISO Abbreviation:  Neurochem. Res.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-30     Completed Date:  1999-03-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  219-26     Citation Subset:  IM    
Eisai Co., Ltd., Tokyo, Japan.
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MeSH Terms
Amyloid beta-Protein / physiology*
Cell Line
G(M1) Ganglioside / physiology*
Interleukin-1 / metabolism*
Interleukin-6 / metabolism*
Monocytes / metabolism
Tumor Necrosis Factor-alpha / metabolism*
Grant Support
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Interleukin-1; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 37758-47-7/G(M1) Ganglioside

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