Similar Normalizing Effect of HSP70 and YB-1 Stress Proteins on the Brain Transcription of a Mouse Model of Alzheimer's Disease.

Previously, we demonstrated the therapeutic effects of intranasal administration of human HSP70 and YB-1 proteins in various models of AD, including olfactory bulbectomized (OBX) mice. Herein, we investigated the effect of these two stress proteins on transcription in the hippocampus and cortex of OBX mice. Despite different structures, both proteins frequently caused pronounced normalizing changes in the transcription of the same genes. Thus, the genes that normalized their expression due to the action of recHSP70 or recYB-1 coincide by 61%. More than 60% of these common target genes exhibited complete restoration to a pattern similar to that of the control sham-operated mice. Notably, the number of genes with altered expression after administration of the proteins was twice as high in the hippocampus as in the cortex. In the brain of OBX mice, the protein application led to a normalization of the expression of many genes related to AD pathogenesis, including genes that participated in the metabolism of Aβ and tau proteins. Importantly, the normalized genes also include loci involved in ribosome biogenesis, as well as genes responsible for neurotransmitter transport, cognition, apoptosis, mitochondrial functions, and protection from oxidative stress. A significant positive effect of both proteins was demonstrated in all six cell types studied in the brain of OBX mice, with the most pronounced effect observed in the astrocytes. Besides AD-related genes, both proteins normalized the expression of several genes implicated in the development of major depression and other neurodegenerative diseases.