Electrochemical detection of Zn(II)- and Cu(II)-induced amyloid-β aggregation: Quantitative aspects and application to amyloid-β isoformsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 20 мая 2017 г.
Аннотация:The tyrosine based electrochemical analysis of the Zn(II)- and Cu(II)-induced aggregation of Aβ42 – the amyloid-β peptide implicated in Alzheimer's disease pathogenesis – and its isoforms with D7H and H6R familial mutations or the naturally occurring Ser-8 phosphorylation was carried out by square wave voltammetry on carbon screen printed electrodes. The electrooxidation peak current was directly compared with the size (determined by dynamic light scattering, DLS) of Aβ42 aggregates formed in the analyzed samples in the presence of Zn(II) or Cu(II) ions (Me(II)) and the amount of peptide in the ‘soluble’ (resistant to sedimentation upon application of centrifugal force) fraction. It was demonstrated that at substoichiometric Me(II) ion concentrations, the decrease of the electrooxidation current with the Me(II) ion concentration may be attributed to depletion of a peptide pool constituting the ‘soluble’ fraction. Above the stoichiometric Me(II) ion concentration, the contribution to the peak current from the large “sedimentation-prone” Aβ42 aggregates starts to progressively dominate. The relative values of the peak current can potentially serve as an estimate of the relative number of ‘soluble’ peptide in Aβ42 preparation. The application of direct electrochemistry to the Me(II)-induced aggregation of Aβ42 isoforms concurrently with DLS has allowed to reveal some specific features of the aggregation process, determined by the presence of mutations and the modification. The direct electrochemistry appears to present itself as a method complementary to methods for monitoring the Me(II)-induced Aβ aggregation based on aggregate detection.