Interaction of serotransferrin and C1-esterase inhibitor with amyloid-β peptide

Nemashkalova, E.; Vologzhannikova, A.; Kazakov, A.; Deryusheva, E.; Shevelyova, M.; Levashov, P.; Shukurov, R.; Litus, E.

Авторы: Nemashkalova E., Vologzhannikova A., Kazakov A., Deryusheva E., Shevelyova M., Levashov P., Shukurov R., Litus E.
Сборник: The 7th Congress of Biophysicists of Russia - conference proceedings, Biophys Rev, 15, 2023, 1425–1861
Серия: The 7th Congress of Biophysicists of Russia - conference proceedings
Том: 15
Год издания: 2023
Место издания: Springer Science and Business Media LLC Германия
Первая страница: 24
Последняя страница: 24
Номер статьи: S1.47
DOI: 10.1007/s12551-023-01150-w
Аннотация: One of the main factors provoking the development of Alzheimer’s disease (AD) is the accumulation of amyloid-beta peptide (Aβ) in the brain. A number of plasma and cerebrospinal fluid proteins have been shown to be powerful inhibitors of Aβ fibrillation, which can be used in AD therapy. Serotransferrin (Tf) and C1-esterase inhibitor (C1I) belong to a group of plasma proteins associated with the pathogenesis of AD. Tf is the main carrier of iron ions in blood plasma. According to some reports, its content in the brain and serum of patients with AD is reduced. C1I plays an important role in the functioning of bloodproteolytic systems and in the regulation of homeostasis under critical conditions. It has been shown that in the brain of patients with ADthere is a lack of activation of C1I expression, which in turn leads toan increase in the activity of the components of the complement systemand contributes to the progression of AD. At the same time, the directinteraction of these proteins with Aβ has been little studied. In our work, we studied the interaction of Tf and C1H with the monomeric form of Aβ, as well as the effect of these proteins on the kinetics of the process of Aβ fibrilation. The interaction of proteins with the monomeric form of Aβ40/42 was quantitatively studied using the method of surface plasmon resonance spectroscopy. A direct interaction of C1I with the monomeric form of Aβ was found, which was not previously described in the literature. Also, the kinetic and equilibrium parameters of the interaction of Tf with the monomeric form of Aβ40/Aβ42 were studied for the first time. The values of the lowest equilibrium dissociation constant obtained after data approximation by the heterogeneousligand model were 1.5*10^(-9) and 7.8*10^(-9) M for the complex with Aβ40 and Aβ42, respectively. Using a fluorescent test with thioflavin T, the kinetics of Aβ fibril formation in the presence of selected proteins was studied. It was shown that Tf and C1I at a concentration of 8 μM effectively inhibit the growth of Aβ40 fibrils. Thus, it can be assumed that the effect of transferrin and C1-esterase inhibitor on the development of AD, among other things, is mediated by direct interaction with Aβ.
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Interaction of serotransferrin and C1-esterase inhibitor with amyloid-β peptideстатья

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