Immunological approach to structural-functional mapping of the membrane receptors

Abstract

In order to study the structural and functional specificity of different fragments of extracellular domains of the membrane receptors, their immunological blockade and analysis of changes in brain function in health and disease were carried out. Effects of the immunization against unstructured fragments of the neurotrophin receptor (p75 NTR) containing binding sites for a nerve growth factor, amyloid-beta, and proneurotrophin were studied. It was shown that immunization of NMRI mice with synthetic peptides with amino-acid residue sequences corresponding to the p75 NTR fragments 86–93 and 146–153 exerted an adverse effect both on the morpho-functional state of the cortical and hippocampal neurons and on the spatial memory of animals. In contrast, the immunization by the p75 NTR synthetic fragment 167–176 was accompanied by an improvement of these characteristics. The results of the structural-functional mapping of the extracellular domain in neuronal membrane receptors in vivo were in line with the published data of the X-ray analysis. The immunological approach developed in this work provides insight into the peculiarities of the receptor functioning in the course of the Alzheimer’s type neurodegeneration process and favors the development of effective immunological ways for selective therapy of the Alzheimer’s disease.