[The influence of beta-amyloid peptide on the functions of excitable tissues: physiological and pathological aspects]

Beta-amyloid peptide (betaAP) is a product of proteolytic cleavage of wide-spread transmembrane amyloid precursor protein. Betaap is physiological oligopeptide, which is present in biological fluids and tissues of healthy human organism at picomolar concentrations. However, excessive production, polymerization and accumulation of betaAP in tissues (first in neural tissue) underlie the pathogenesis of a number of neurodegenerative diseases (Alzheimer's disease and others). Although the presence of insoluble deposits of fibrillar betaAP (senile plaques) is a characteristic histopathological sign of Alzheimer's disease, soluble betaAP oligomers (dimers, trimers, etc.) possess most neurotoxicity. Soluble betaAP induces mitochondrial dysfunction, increased production of reactive oxygen species in neurons, disorganization of cell plasma membranes, disturbances of ion transport across cell membranes, impairment of synaptic transmission and long-term synaptic plasticity, etc. Recently a lot of attention is paid to possible peripheral effects of betaAP, related to its toxic influence on excitable structures of neuromuscular apparatus and cardiovascular system. At current review we represented state-of-art views on the processes of production and aggregation of betaAP in organism, cellular and molecular mechanisms of betaAP influence on physiological functions of excitable cells, the role of betaAP in pathogenesis of neurodegenerative diseases (Alzheimer's disease and others), as well as the results of our own studies in this field.