MODERN VIEWS ON THE ROLE OF LYSOSOMAL PROTEINAS IN THE PATHOGENESIS OF ALZHEIMERS DISEASE

Alzheimers disease is one of the most common neurodegenerative diseases in the world. The study of the molecular mechanisms of this pathology lasts more than a hundred years, but a single concept of pathogenesis has not yet been developed. The most common theory of the «amyloid cascade», according to which excessive deposition of amyloid (a polypeptide derived from amyloid precursor protein) triggers a number of pathological mechanisms, including hyperphosphorylation of tau protein, which normally is responsible for the stabilization of neuronal microtubules. Like all proteins, amyloid and tau are subject to proteolysis, therefore, the study of the activity of various cathepsins is promising both in terms of identifying the molecular mechanisms of pathogenesis and in terms of the further use of activators or inhibitors of these enzymes as drugs in Alzheimers disease. Among cysteine cathepsins, the contribution of cathepsin B to the progression of Alzheimers disease is the most studied, but the accumulated few data are rather contradictory. On the one hand, with an increase in cathepsin B activity, the synthesis of one of the most pathogenic forms of amyloid, pyroglutamate-amyloid, increases. In other studies, the protective role of this enzyme has been proven. A promising direction is to study the activity of cathepsins in Alzheimers disease, not only in brain tissues obtained by autopsy, and cerebrospinal fluid, but also in tissues readily available for in vivo diagnosis, for example in blood cells.