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Interaction of serotransferrin and C1-esterase inhibitor with amyloid-β peptideстатья
- Авторы: Nemashkalova E., Vologzhannikova A., Kazakov A., Deryusheva E., Shevelyova M., Levashov P., Shukurov R., Litus E.
- Журнал: Biophysical Reviews
- Том: 15
- Номер: 5
- Год издания: 2023
- Издательство: Springer Verlag
- Местоположение издательства: Germany
- 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 fuid proteins have been shown to be powerful inhibitors of Aβ fbrillation, 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 blood proteolytic systems and in the regulation of homeostasis under critical conditions. It has been shown that in the brain of patients with AD there is a lack of activation of C1I expression, which in turn leads to an increase in the activity of the components of the complement system and contributes to the progression of AD. At the same time, the direct interaction 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 efect of these proteins on the kinetics of the process of Aβ fbrilation. 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 frst time. The values of the lowest equilibrium dissociation constant obtained after data approximation by the heterogeneous ligand model were 1.5*10^(-9) and 7.8*10^(-9) M for the complex with Aβ40 and Aβ42, respectively. Using a fuorescent test with thiofavin T, the kinetics of Aβ fbril formation in the presence of selected proteins was studied. It was shown that Tf and C1I at a concentration of 8 μM efectively inhibit the growth of Aβ40 fbrils. Thus, it can be assumed that the efect of transferrin and C1-esterase inhibitor on the development of AD, among other things, is mediated by direct interaction with Aβ.
- Добавил в систему: Левашов Павел Андреевич