ИСТИНА

Amyloid-β (Aβ) is a 39–42 amino acid long peptide found in a cerebrospinal fluid at nanomolar concentrations [1]. According to the amyloid cascade hypothesis, the transition of Aβ from the monomeric state to insoluble fibrillary aggregates, which constitute amyloid plaques, is a key event of Alzheimer’s disease. Details of the molecular mechanism underlying this process are still unclear. It is known that Aβ aggregation can be induced by metal ions which interact with the peptide through its metal-binding domain composed of N-terminal residues 1–16 [2]. In the cerebral cortex, senile plaques are mostly composed by Aβ and contain large amounts of metal ions, such as copper, iron, and zinc. Electrochemical oxidation of synthetic Aβ peptides, viz. Aβ42, Aβ16, and their mutants, was investigated on carbon screen printed electrodes by cyclic and square wave voltammetry. Electrooxidation peaks at potentials of 0.6, 1.05, and a wave at about 1–1.5 V were registered and assigned, respectively, to Tyr-10, His (-6, -13, -14), and Met-35 residues of the Aβ [3, 4]. The peak caused by Tyr residue oxidation was used for detection of Aβ16 interactions with metal ions [5, 6], of Aβ42 aggregation [7, 8], and of Aβ16 post-translational modifications (PTMs). The addition of both Zn(II) and Cu(II) ions significantly reduced the intensity of Aβ16 Tyr oxidation signal and shifted the peak to more positive potentials, while Mg(II) and Ca(II) ions had no noticeable effect. The decrease of electrooxidation current with Aβ42 aggregation was attributed to a depletion of peptide pool constituting the ‘soluble’ fraction. Electrochemical analysis of Aβ16, Aβ42 and its mutants allowed for distinguishing: (i) some mutants under study from the ‘normal variant’ of the Aβ; and (ii) the mutants from one another [4, 6]. In addition, O-phosphorylation of Tyr-10 and Ser-8 and 3-nitration of Tyr-10 residues of Aβ16 was found to strongly influence peptide’s electrochemical properties [9]. The proposed direct electrochemical assays appear to be very promising for studying peptides aggregation and complexing with metal ions as well as peptides’ PTMs. This work was financially supported by the Russian Science Foundation, grant 14-24-00100. [1] P.D. Mehta, T. Pirttila, S.P. Mehta, E.A. Sersen, P.S. Alsen, H.M. Wisniewski, Plasma and Cerebrospinal Fluid Levels of Amiloid β Proteins 1-40 and 1-42 in Alzheimer Disease, Arch. Neurol. 57 (2000) 100. [2] P. Faller, C. Hureau, O. Berthoumieu, Role of metal ions in the self-assembly of the Alzheimer's amyloid-beta peptide, Inorg. Chem. 52 (2013) 12193. [3] E.V. Suprun, S.A. Khmeleva, S.P. Radko, S.A. Kozin, A.I. Archakov, V.V. Shumyantseva, Direct electrochemical oxidation of amyloid-β peptides via tyrosine, histidine, and methionine residues, Electrochem. Commun. 65 (2016) 53. [4] E.V. Suprun, S.P. Radko, S.A. Khmeleva, V.A. Mitkevich, A.I. Archakov, A.A. Makarov, V.V. Shumyantseva, Electrochemical oxidation of amyloid-beta peptide isoforms on carbon screen printed electrodes, Electrochem. Commun. 75 (2017) 33. [5] E.V. Suprun, N.V. Zaryanov, S.P. Radko, A.A. Kulikova, S.A. Kozin, A.A. Makarov, A.I. Archakov, V.V. Shumyantseva, Tyrosine Based Electrochemical Analysis of Amyloid-β Fragment (1-16) Binding to Metal(II) Ions, Electrochim. Acta 179 (2015) 93. [6] E.V. Suprun, S.A. Khmeleva, S.P. Radko, A.I. Archakov, V.V. Shumyantseva, Electrochemical Analysis of Amyloid-β Domain 1-16 Isoforms and Their Complexes with Zn(II) Ions, Electrochim. Acta 187 (2016) 677. [7] E.V. Suprun, S.A. Khmeleva, Y.Y. Kiseleva, S.P. Radko, A.I. Archakov, V.V. Shumyantseva, Quantitative Aspects of Electrochemical Detection of Amyloid-β Aggregation, Electroanalysis 28. (2016) 1977. [8] E.V. Suprun, S.P. Radko, E.A. Andreev, S.A. Khmeleva, S.A. Kozin, A.A. Makarov, A.I. Archakov, V.V. Shumyantseva, Electrochemical detection of Zn(II)- and Cu(II)-induced amyloid-β aggregation: Quantitative aspects and application to amyloid-β isoforms, J. Electroanal. Chem. 791 (2017) 152. [9] E.V. Suprun, S.P. Radko, T.E. Farafonova, S.A. Kozin, A.A. Makarov, A.I. Archakov, V.V. Shumyantseva, Electrochemical detection of protein post-translational modifications: Phosphorylation and nitration of amyloid-beta (1–16), Electrochim. Acta 258 (2017) 1182.