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Alzheimer's Disease: NMR Studies of Asialo (GM1) and Trisialo (GT1b) Ganglioside Interactions with Aβ(1-40) Peptide in a Membrane Mimic Environment

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Abstract

Amyloid peptide (Aβ) is the major protein constituent of neuritic plaques in Alzheimer's disease (AD). This peptide is an amphipathic molecule that perturbs membranes and binds to raft-like membranes composed of gangliosides. Ganglioside GM1 binds tightly with Aβ and it is speculated that GM1 inhibits Aβ from undergoing α-helix to β-sheet conformational changes. Although the role of gangliosides in conformational changes of Aβ have been studied, the specific nature of these interactions have not been reported. In the present report multidimensional NMR studies of ganglioside-Aβ interactions were conducted in sodium dodecyl sulphate (SDS) micelles, a membrane-mimicking environment. These studies reveal that asialoGM1 binds specifically with Aβ in a manner which could prevent β-sheet formation, but that ganglioside GT1b does not bind Aβ. Plausible pathways for the involvement of gangliosides in amyloidogenesis are discussed.

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Authors and Affiliations

  1. Laboratory of Neurophysics, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania

    Pravat K. Mandal & Jay W. Pettegrew

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  1. Pravat K. Mandal
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  2. Jay W. Pettegrew
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Correspondence to Jay W. Pettegrew.

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Mandal, P.K., Pettegrew, J.W. Alzheimer's Disease: NMR Studies of Asialo (GM1) and Trisialo (GT1b) Ganglioside Interactions with Aβ(1-40) Peptide in a Membrane Mimic Environment. Neurochem Res 29, 447–453 (2004). https://doi.org/10.1023/B:NERE.0000013750.80925.25

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  • DOI: https://doi.org/10.1023/B:NERE.0000013750.80925.25

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