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Zinc-induced dimers of chemically modified Aβ are possible aggregation seedsстатья Тезисы
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или ScopusДата последнего поиска статьи во внешних источниках: 28 мая 2015 г.
- Авторы: Kozin Sergey A., Philippe Tsvetkov, Alexandra Kulikova, Maria Indeikina, Yuri Mezentsev, Andrey Istrate, Igor Popov, Alexis Ivanov, Vladimir Polshakov, Alexander Makarov
- Журнал: Alzheimer's and Dementia
- Том: 10
- Номер: 4
- Год издания: 2014
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: P793
- DOI: 10.1016/j.jalz.2014.05.1542
- Аннотация: Zinc ions are necessary for Aβ aggregation in vivo. Region 1-16 constitutes the metal-binding domain of human Aβ, and amino acids 6-14 form the minimal zinc-binding site. Zinc-dependent Aβ dimerization is mediated by a tetrapeptide stretch 11-14. Isomerization of Asp7, the most abundant aging-associated spontaneous chemical modification of Aβ, makes the resulting isoAsp7-containing Aβ (isoAβ) much more susceptible to Zn-bound dimerization with dimers serving as aggregation seeds. Indeed, it has been shown in experiments on transgenic mice that intravenous injections of isoAβ cause a sharp increase in the number (up to 9 times) of congophilic amyloid plaques in the brain compared to their intact littermates. In the present study we show the influence of Ser-8 phosphorilation and H6R mutation on the formation of potentially pathogenic zinc-induced Aβ dimers. The obtained data show that the Aβ species in which the 11-14 stretch is more accessible for intermolecular interactions due to specific chemical modifications or mutations in the region 6-10 can act as triggers for zinc-induced aggregation of Aβ. These results suggest that the information on three-dimensional structure of the Zn-binding interface of the dimers can be used for rational drug design, targeting Alzheimer's disease.
- Добавил в систему: Польшаков Владимир Иванович