Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges.

ABSTRACT: To completely treat and ultimately prevent dementia, it is essential to elucidate its pathogenic mechanisms in detail. There are two major hypotheses for the pathogenesis of Alzheimer's dementia: the β-amyloid (Aβ) hypothesis and the tau hypothesis. The modified amyloid hypothesis, which proposes that toxic oligomers rather than amyloid fibrils are the essential cause, has recently emerged. Aβ peptides [Aβ(1-40) and Aβ(1-42)] form highly insoluble aggregates in vivo and in vitro. These Aβ aggregates contain many polymorphisms, whereas Aβ peptides are intrinsically disordered in physiological aqueous solutions without any compact conformers. Over the last three decades, solid-state nuclear magnetic resonance (NMR) has greatly contributed to elucidating the structure of each polymorph, while

SUBMITTER: Hiroaki H 

PROVIDER: S-EPMC10205579 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature