Recent Advances by In Silico and In Vitro Studies of Amyloid-? 1-42 Fibril Depicted a S-Shape Conformation.

ABSTRACT: The amyloid-? 1-42 (A?1-42) peptide is produced by proteolytic cleavage of the amyloid precursor protein (APP) by sequential reactions that are catalyzed by ? and ? secretases. A?1-42, together with the Tau protein are two principal hallmarks of Alzheimer's disease (AD) that are related to disease genesis and progression. A?1-42 possesses a higher aggregation propensity, and it is able to form fibrils via nucleated fibril formation. To date, there are compounds available that prevent A?1-42 aggregation, but none have been successful in clinical trials, possibly because the A?1-42 structure and aggregation mechanisms are not thoroughly understood. New molecules have been designed, employing knowledge of the A?1-42 structure and are based on preventing or breaking the ionic interactions that have been proposed for formation of the A?1-42 fibril U-shaped structure. Recently, a new A?1-42 fibril S-shaped structure was reported that, together with its aggregation and catalytic properties, could be helpful in the design of new inhibitor molecules. Therefore, in silico and in vitro methods have been employed to analyze the A?1-42 fibril S-shaped structure and its aggregation to obtain more accurate A?1-42 oligomerization data for the design and evaluation of new molecules that can prevent the fibrillation process.

SUBMITTER: Villalobos Acosta DMA 

PROVIDER: S-EPMC6121414 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature