Role of Hydrophobicity at the N-Terminal Region of Aβ42 in Secondary Nucleation.

ABSTRACT: The self-assembly of the amyloid β 42 (Aβ42) peptide is linked to Alzheimer's disease, and oligomeric intermediates are linked to neuronal cell death during the pathology of the disease. These oligomers are produced prolifically during secondary nucleation, by which the aggregation of monomers is catalyzed on fibril surfaces. Significant progress has been made in understanding the aggregation mechanism of Aβ42; still, a detailed molecular-level understanding of secondary nucleation is lacking. Here, we explore the role of four hydrophobic residues on the unstructured N-terminal region of Aβ42 in secondary nucleation. We create eight mutants with single substitutions at one of the four positions─Ala2, Phe4, Tyr10, and Val12─to decrease the hydrophobicity at respective positions (A2T, A2S, F

SUBMITTER: Thacker D 

PROVIDER: S-EPMC9732875 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature