title: The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.
abstract: 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.
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: N V
authors.initials: NV
authors.lastname: Bobkova
authors.affiliation: Institute of Protein Research, RAS, Pushchino, Moscow Region, Russia.
authors.forename: D N
authors.initials: DN
authors.lastname: Lyabin
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: N I
authors.initials: NI
authors.lastname: Medvinskaya
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: A N
authors.initials: AN
authors.lastname: Samokhin
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: P V
authors.initials: PV
authors.lastname: Nekrasov
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Nesterova
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: I Y
authors.initials: IY
authors.lastname: Aleksandrova
authors.affiliation: Institute of Cell Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: O G
authors.initials: OG
authors.lastname: Tatarnikova
authors.affiliation: Institute of Theoretical and Experimental Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: A G
authors.initials: AG
authors.lastname: Bobylev
authors.affiliation: Institute of Theoretical and Experimental Biophysics, RAS, Pushchino, Moscow Region, Russia.
authors.forename: I M
authors.initials: IM
authors.lastname: Vikhlyantsev
authors.affiliation: Institute of Physiologically Active Compounds, RAS, Chernogolovka, Moscow Region, Russia.
authors.forename: M S
authors.initials: MS
authors.lastname: Kukharsky
authors.affiliation: Institute of Physiologically Active Compounds, RAS, Chernogolovka, Moscow Region, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Ustyugov
authors.affiliation: Institute of Protein Research, RAS, Pushchino, Moscow Region, Russia.
authors.forename: D N
authors.initials: DN
authors.lastname: Polyakov
authors.affiliation: Institute of Protein Research, RAS, Pushchino, Moscow Region, Russia.
authors.forename: I A
authors.initials: IA
authors.lastname: Eliseeva
authors.affiliation: Institute of Protein Research, RAS, Pushchino, Moscow Region, Russia.
authors.forename: D A
authors.initials: DA
authors.lastname: Kretov
authors.affiliation: Institute of Protein Research, RAS, Pushchino, Moscow Region, Russia.
authors.forename: S G
authors.initials: SG
authors.lastname: Guryanov
authors.affiliation: Institute of Protein Research, RAS, Pushchino, Moscow Region, Russia.
authors.forename: L P
authors.initials: LP
authors.lastname: Ovchinnikov
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009830:Olfactory Bulb / Q000601:surgery; D010446:Peptide Fragments / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology*; D051840:Y-Box-Binding Protein 1 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D051840:Y-Box-Binding Protein 1; C075222:amyloid beta-protein (1-42)