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

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-1(1-219), 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 b-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 b-amyloid (1-42) inhibited formation of a-amyloid fibrils, as confirmed by electron microscopy. This suggests that Yb-1 interaction with a-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.