Assembly of Alzheimer-like, insoluble filaments from brain cerebrosides.
Amphiphiles are molecules which contain a polar head and a hydrophobic tail. When the head contains a chiral center, amphiphiles, incubated in the presence of some di- and trivalent metal ions, have been shown to form large fibrous molecular aggregates. In this study, naturally occurring brain cerebroside was tested to determine if it had sufficient amphiphilic properties to form similar supramolecular structures. When galactocerebroside was heated in the presence of magnesium, it was able to form tubules, vesicles and filaments. The filaments included long fibrils that aggregated into dense bundles and short fibrils that were associated to form smaller bundles. These fibrils were shown to be resistant to solubilization in boiling SDS in the presence of reducing agents. This is the first report of a naturally occurring glycolipid being able to form filaments. Since their structural and physical properties are similar to the paired helical filaments of Alzheimer's disease, they may serve as an experimental model for their assembly.
Goux
W J
WJ
Department of Chemistry, University of Texas at Dallas, Richardson 75083-0688, USA.
Smith
H
H
Sparkman
D R
DR
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry; D002554:Cerebrosides / Q000378:metabolism*; D005699:Galactosylceramides / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism*
D002554:Cerebrosides; D005699:Galactosylceramides; C002454:galactocerebroside; D008274:Magnesium