Parallel in-register contact propensity predicts the Amyloidogenicity of ADan and ABri in familial dementias.

ABSTRACT: Familial Danish dementia (FDD) and British dementia (FBD) are rare neurodegenerative diseases caused by stop-codon mutations in the Bri2 gene, leading to amyloid deposits formed by the aggregation of mutant ADan and ABri peptides, respectively. FDD symptoms usually manifest decades earlier than those of FBD. Probably due to the rarity of these conditions, the aggregation mechanisms of ADan and ABri and the molecular basis for FDD's earlier onset remain underexplored. Here, we computationally investigated the conformational dynamics of monomeric wild-type Bri23 and the two mutants ADan and ABri, as well as their self-assembly dynamics from dimers to hexamers using atomistic discrete molecular dynamics simulations. Our results aligned with earlier experimental work on the monomeric structure

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC12817262 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature