Pathogenic Aβ A2V versus protective Aβ A2T mutation : early stage aggregation and membrane interaction
Articolo
Data di Pubblicazione:
2017
Citazione:
Pathogenic Aβ A2V versus protective Aβ A2T mutation : early stage aggregation and membrane interaction / L. Colombo, A. Gamba, L. Cantù, M. Salmona, F. Tagliavini, V. Rondelli, E. Del Favero, P. Brocca. - In: BIOPHYSICAL CHEMISTRY. - ISSN 0301-4622. - 229(2017 Oct), pp. 11-18. [10.1016/j.bpc.2017.05.001]
Abstract:
We investigated the effects of punctual A-to-V and A-to-T mutations in the amyloid precursor protein APP, corresponding to position 2 of Aβ1–42. Those mutations had opposite effects on the onset and progression of Alzheimer disease, the former inducing early AD pathology and the latter protecting against the onset of the disease. We applied Static and Dynamic Light Scattering and Circular Dichroism, to study the different mutants in the early stages of the aggregation process, essential for the disease. Comparative results showed that the aggregation pathways differ in the kinetics and extent of the process, in the size of the aggregates and in the evolution of the secondary structure, resulting in fibrils of different morphology, as seen by AFM. Mutated peptides had comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering, all of them displayed disordering effects on the internal structure of mixed phospholipids-gangliosides model membranes.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Aβ1–42 peptide; A2V; A2T; Aβ aggregation; Aβ membrane interaction; Laser light scattering; X-ray scattering
Elenco autori:
L. Colombo, A. Gamba, L. Cantù, M. Salmona, F. Tagliavini, V. Rondelli, E. Del Favero, P. Brocca
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