Aggregation Mechanism of Alzheimer's Amyloid ?-Peptide Mediated by ?-Strand/?-Sheet Structure.

ABSTRACT: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and a widespread form of dementia. Aggregated forms of the amyloid ?-peptide (A?) are identified as a toxic species responsible for neuronal damage in AD. Extensive research has been conducted to reveal the aggregation mechanism of A?. However, the structure of pathological aggregates and the mechanism of aggregation are not well understood. Recently, experimental studies have confirmed that the ?-sheet structure in A? drives aggregation and toxicity in AD. However, how the ?-sheet structure is formed in A? and how it contributes to A? aggregation remains elusive. In the present study, molecular dynamics simulations suggest that A? adopts the ?-strand conformation by peptide-plane flipping. Multiple ?-strands interact through hydrogen bonding to form ?-sheets. This structure acts as a nucleus that initiates and promotes aggregation and fibrillation of A?. Our findings are supported by previous experimental as well as theoretical studies. This study provides valuable structural insights for the design of anti-AD drugs exploiting the ?-strand/?-sheet structure.

SUBMITTER: Balupuri A 

PROVIDER: S-EPMC7038184 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature