Single point mutations in the Alzheimer's disease associated Aβ42 peptide are found to alter significantly its neurotoxic properties in vivo and have been associated with early onset forms of this devastating condition. We show that such mutations can induce structural changes in Aβ42 fibrils and are associated with a dramatic switch in the fibril-dependent mechanism by which Aβ42 aggregates. These observations reveal how subtle perturbations to the physicochemical properties of the Aβ peptide, and the structural properties of fibrils that it forms, can have profound effects on the mechanism of its aggregation and pathogenicity. © 2013 American Chemical Society.
Bolognesi, B., Cohen, S., Aran Terol, P., Esbjörner, E., Giorgetti, S., Mossuto, M., et al. (2014). Single point mutations induce a switch in the molecular mechanism of the aggregation of the Alzheimer's disease associated Aβ42 peptide. ACS CHEMICAL BIOLOGY, 9(2), 378-382 [10.1021/cb400616y].
Single point mutations induce a switch in the molecular mechanism of the aggregation of the Alzheimer's disease associated Aβ42 peptide
NATALELLO, ANTONINO;
2014
Abstract
Single point mutations in the Alzheimer's disease associated Aβ42 peptide are found to alter significantly its neurotoxic properties in vivo and have been associated with early onset forms of this devastating condition. We show that such mutations can induce structural changes in Aβ42 fibrils and are associated with a dramatic switch in the fibril-dependent mechanism by which Aβ42 aggregates. These observations reveal how subtle perturbations to the physicochemical properties of the Aβ peptide, and the structural properties of fibrils that it forms, can have profound effects on the mechanism of its aggregation and pathogenicity. © 2013 American Chemical Society.
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