title: [Identification of the minimal zinc-binding center in natural isoforms of amyloid-beta domain 1-16 using ESI-MS].
abstract: Alzheimer's disease, is a lethal neurodegenerative pathology, characterized by the formation of soluble neurotoxic oligomers of the human amyloid-beta peptide Abeta which get accumulated forming polymeric extracellular aggregates (so-called amyloid plaques). The isomerized at aspartate 7 isoform of the human Abeta (isoAbeta) is the main component of these plaques and is considered as the potential pathogenic agent of AD. Besides this, there is a possible generation mechanism for this isoform from a genetically deficient D7N Abeta variant (Tottori mutation). On the contrary the rodent Abeta (rat Abeta), which has three amino acid substitutions in its metal-binding domain, is not susceptible to pathogenic aggregation in vivo, unlike the other known natural isoforms of Abeta. Interactions with zinc ions play a crucial role in the aggregation of monomeric human Abeta in vitro and in vivo. In the presented article using high resolution ESI-MS methods it was shown that domains 1-16 of isoAbeta and D7NAbeta bind zinc ions in the exactly the same manner as the normal human Abeta1-16, whereas ratAbeta has significant differences in structure of its minimal zinc binding center. These results confirm the overall interaction mechanism between zinc ions and the humanAbeta isoforms and allows to suppose that perhaps modulation of the structure of region 6-14 of Abeta can be used as a promising therapeutic approach to AD treatment.
authors.forename: I A
authors.initials: IA
authors.lastname: Popov
authors.forename: M I
authors.initials: MI
authors.lastname: Indeĭkina
authors.forename: A S
authors.initials: AS
authors.lastname: Kononikhin
authors.forename: N L
authors.initials: NL
authors.lastname: Starodubtseva
authors.forename: S A
authors.initials: SA
authors.lastname: Kozin
authors.forename: A A
authors.initials: AA
authors.lastname: Makarov
authors.forename: E N
authors.initials: EN
authors.lastname: Nikolaev
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D006801:Humans; D013058:Mass Spectrometry; D020033:Protein Isoforms / Q000737:chemistry; D051381:Rats; D013045:Species Specificity; D015032:Zinc / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D020033:Protein Isoforms; D015032:Zinc