ИСТИНА

Olfactory bulbectomized (OBX) mice are widely utilized as a model of sporadic Alzheimer’s disease (AD) because develop some major characteristics similar to AD neurodegeneration. It is known that activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of AD. Soluble oligomeric amyloid beta (Abeta) binds to the V-domain of RAGE which mediates neurotoxic effect of Abeta species on neurons and microglia. Presumably, synthetic peptide fragments from surface-exposed regions of the V-domain can interact with Abeta as a decoy, acting as a cytoprotective agent against neurodegeneration. We investigated the impairments of neuronal mitochondria and spatial memory in OBX mice, and also studied the therapeutic action of peptide fragments of RAGE. Dysfunction of mitochondrial metabolism and inhibition of the activity of respiratory chain complexes I and IV were detected in mitochondria of the neocortex and hippocampus in OBX mice. Deficiency of metabolism was accompanied by loss of spatial memory and an increase in the level of Abeta(1-40) in the brain. Peptide fragments corresponding to the nonstructural region of the RAGE ectodomain were synthesized and tested as therapeutic substances. From all peptides tested, only one showed a significant positive effect, namely the fragment (60-76). Intranasal administration of this fragment for 3 weeks prevented the memory loss of OBX mice, reactivated the mitochondrial respiratory chain complexes. As a result, the synthetic peptide fragment (60-76) of RAGE can serve as a promising therapeutic agent against AD development. This study was supported by grant from the RFBR No.16-04-00944.