Role of apoptosis-associated proteins p53 and bcl-2 in the pathogenesis of nervous system diseases

Abstract

Diseases of the central nervous system occupy a leading place, along with cardiovascular and oncological diseases, and the proportion of patients suffering from diseases of the nervous system is increasing as the population ages. This group of diseases includes acute conditions, such as ischemic stroke, and chronic multifactorial diseases — Alzheimer's and Parkinson's diseases, epilepsy, etc. The development of specific methods for their treatment is difficult, and these drugs are not very effective. Almost all brain diseases are based on common mechanisms such as oxidative stress, inflammation and neuronal death. Most often, cells die by apoptosis due to an imbalance between pro-apoptotic and anti-apoptotic factors. This work examines two of them: the apoptosis-promoting transcription factor and tumor suppressor p53 and its opposing B-cell lymphoma protein Bcl-2. The choice of these proteins for study is due to the fact that both proteins are key regulators of apoptosis and are important in the pathogenesis of nervous diseases, since neurons are not highly proliferating cells. The p53 protein is involved in the regulation of many genes responsible for DNA repair, apoptosis, and other biochemical cellular processes; this is especially important when studying neuronal pathology. Bcl-2 suppresses apoptosis in various cells, including neurons, by controlling mitochondrial membrane permeability and inhibiting caspases. In diseases, its expression can either increase, for example, in the case of malignant tumors, or decrease, as in the case of neurodegenerative processes. It has been established that p53 and Bcl-2 are in close interaction in the process of regulating apoptosis; their ratio may be an important prognostic factor. The purpose of this work was to assess the role of these proteins in the pathogenesis of various diseases of the nervous system, and to search for general patterns of changes in their expression and coexpression.