Pathological conditions associated with tau protein: mechanisms of development and possible biological targets for pharmacological correction of tau proteinopathy (review)

Abstract

Background: The pathological process associated with the pathogenic aggregation of tau is called taupathy. The same term is often used to refer to a group of neurodegenerative diseases, an important pathogenetic component of which is the aggregation of tau. A violation in the expression of the MART gene leads to changes in the physicochemical properties of the protein. Modern strategies for the search for therapeutic agents to modulate tau-proteinopathy are aimed at creating drugs that suppress the formation of pathogenic forms of protein and its aggregation, but at the same time do not disrupt the metabolism of normal intracellular tau and its function in stabilizing microtubules. The aim of the study:To consider possible biological targets of pathological conditions associated with tau protein and to identify ways of pharmacological correction of tau proteinopath. Materials and methods:We analyzed the literature on the main mechanisms of pathological conditions associated with tau protein and possible biological targets for pharmacological correction of tau-proteinopathy published over the last 10 years. Results: Modern strategies for the search for therapeutic agents to modulate tau-proteinopathy, including Alzheimer's disease, are aimed at creating drugs that suppress the formation of pathogenic forms of tau and its aggregation, but do not disrupt the metabolism of normal intracellular tau protein and its function in stabilizing microtubules. In this regard, the search for therapeutic agents capable of correcting tau-proteinopathy has significantly intensified. Conclusion: There are several approaches to the treatment and prevention of tau-proteinopathy. Stabilization of the microtubule structure, reduction of the activity of full-sized and hyperphosphorylated tau, regulation of pathological phosphorylation of tau, prevention of protein aggregation, inhibition of abnormal aggregation, prevention of oligomerization, inhibition of accumulation inside the cell, specific inhibition of purinoreceptor P2RX7, regulation of AMPA receptors, blocking penetration into cells and transmission of pathogenic protein.