Cross-seeding of wild-type and hereditary variant-type amyloid beta-proteins in the presence of gangliosides.
We investigated the molecular mechanism underlying the ganglioside-induced initiation of the assembly of wild and hereditary variant-type amyloid beta-proteins, including Arctic-, Dutch-, and Flemish-type amyloid beta-proteins. We monitored the assembly of amyloid beta-protein by thioflavin-T assay, western blotting and electron microscopy. We also examined how externally added amyloid beta-protein assembles in a cell culture. The assembly of wild-, Arctic-, Dutch-, and Flemish-type amyloid beta-proteins were accelerated in the presence of GM1, GM1, GM3 and GD3 gangliosides. Notably, all of these amyloid beta-proteins accelerated the assembly of different type of amyloid beta-protein, following prior binding to a specific ganglioside. A specific-ganglioside-bound form of variant-type amyloid beta-protein was recognized by the antibody (4396C) specific to the GM1-ganglioside-induced altered conformation of wild-type amyloid beta-protein. Moreover, the assembly of these amyloid beta-proteins in the presence of a specific ganglioside was markedly suppressed by coincubation with 4396C. This study suggests that cross-seeding can occur between wild and hereditary variant-type amyloid beta-proteins despite differences in their amino acid sequences.
Yamamoto
Naoki
N
Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Morioka, Obu, Japan.
Matsuzaki
Katsumi
K
Yanagisawa
Katsuhiko
K
D016229:Amyloid beta-Peptides / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005733:Gangliosidoses / Q000145:classification / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D008081:Liposomes / Q000378:metabolism; D008855:Microscopy, Electron, Scanning / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D009439:Neuraminidase / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008081:Liposomes; C052635:cholera toxin, B subunit-horseradish peroxidase; D002772:Cholera Toxin; D006735:Horseradish Peroxidase; D009439:Neuraminidase