Co-aggregation of α-synuclein with amyloid-β stabilizes β-sheet-rich oligomers and enhances the formation of β-barrels.

ABSTRACT: Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases with markedly different pathological features of β-amyloid (Aβ) plaques and α-synuclein (αS) Lewy bodies (LBs), respectively. However, clinical overlaps in symptoms and pathologies between AD and PD are commonly observed caused by the cross-interaction between Aβ and αS. To uncover the molecular mechanisms behind their overlapping symptoms and pathologies, we computationally investigated the impact of αS on an Aβ monomer and dimerization using atomistic discrete molecular dynamics simulations (DMD). Our results revealed that αS could directly interact with Aβ monomers and dimers, thus forming β-sheet-rich oligomers, including potentially toxic β-barrel intermediates. The binding hotspot

SUBMITTER: Huang F 

PROVIDER: S-EPMC10704842 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature