The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models

Bobkova, N.V.; Lyabin, D.N.; Medvinskaya, N.I.; Samokhin, A.N.; Nekrasov, P.V.; Nesterova, I.V.; Aleksandrova, I.Y.; Tatarnikova, O.G.; Bobylev, A.G.; Vikhlyantsev, I.M.; Kukharsky, M.S.; Ustyugov, A.A.; Polyakov, D.N.; Eliseeva, I.A.; Kretov, D.A.; Guryanov, S.G.; Ovchinnikov, L.P.

Авторы: Bobkova N.V., Lyabin D.N., Medvinskaya N.I., Samokhin A.N., Nekrasov P.V., Nesterova I.V., Aleksandrova I.Y., Tatarnikova O.G., Bobylev A.G., Vikhlyantsev I.M., Kukharsky M.S., Ustyugov A.A., Polyakov D.N., Eliseeva I.A., Kretov D.A., Guryanov S.G., Ovchinnikov L.P.
Журнал: PLoS ONE
Том: 10
Номер: 9
Год издания: 2015
Издательство: Public Library of Science
Местоположение издательства: United States
Первая страница: e0138867
DOI: 10.1371/journal.pone.0138867
Аннотация: The Y-box binding protein 1 (YB-1) is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX) mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42) inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.
Добавил в систему: Лябин Дмитрий Николаевич

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The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Modelsстатья