Polymorphic C-terminal beta-sheet interactions determine the formation of fibril or amyloid beta-derived diffusible ligand-like globulomer for the Alzheimer Abeta42 dodecamer.

ABSTRACT: The relationship between amyloid deposition and cellular toxicity is still controversial. In addition to fibril-forming oligomers, other soluble Aβ forms (amyloid β-derived diffusible ligands (ADDLs)) were also suggested to form and to present different morphologies and mechanisms of toxicity. One ADDL type, the "globulomer," apparently forms independently of the fibril aggregation pathway. Even though many studies argue that such soluble Aβ oligomers are off fibril formation pathways, they may nonetheless share some structural similarity with protofibrils. NMR data of globulomer intermediates, "preglobulomers," suggested parallel in-register C-terminal β-sheets, with different N-terminal conformations. Based on experimental data, we computationally investigate four classes of Aβ dodecamer

SUBMITTER: Ma B 

PROVIDER: S-EPMC2978638 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature