Alzheimer's disease: NMR studies of asialo (GM1) and trisialo (GT1b) ganglioside interactions with Abeta(1-40) peptide in a membrane mimic environment.
Amyloid peptide (Abeta) 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 Abeta and it is speculated that GM1 inhibits Abeta from undergoing alpha-helix to beta-sheet conformational changes. Although the role of gangliosides in conformational changes of Abeta have been studied, the specific nature of these interactions have not been reported. In the present report multidimensional NMR studies of ganglioside-Abeta interactions were conducted in sodium dodecyl sulphate (SDS) micelles, a membrane-mimicking environment. These studies reveal that asialoGM1 binds specifically with Abeta in a manner which could prevent beta-sheet formation. but that ganglioside GT1b does not bind Abeta. Plausible pathways for the involvement of gangliosides in amyloidogenesis are discussed.
Laboratory of Neurophysics, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA.
Pravat K
PK
Mandal
Jay W
JW
Pettegrew
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism*; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate
D016229:Amyloid beta-Peptides; D005732:Gangliosides; D008823:Micelles; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012967:Sodium Dodecyl Sulfate; D005677:G(M1) Ganglioside; C016481:trisialoganglioside GT1; C018835:asialo GM1 ganglioside