Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aß42 peptide.
Nat Chem
; 12(5): 445-451, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32284577
ABSTRACT
Oligomeric species populated during the aggregation of the Aß42 peptide have been identified as potent cytotoxins linked to Alzheimer's disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aß42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aß42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Péptidos beta-Amiloides
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Nat Chem
Asunto de la revista:
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido