Role of Apoptosis-Related 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 them is increasing as the population ages. This group of diseases encompasses acute conditions, such as ischemic stroke, and chronic multifactorial diseases, e.g., Alzheimer’s and Parkinson’s diseases, epilepsy, etc. The development of specific methods for their treatment is difficult, while the efficacy of the available drugs is quite low. Almost all brain diseases are underlain by common mechanisms, such as oxidative stress, inflammation, and neuronal death. Most often, cells die through apoptosis caused by an imbalance of pro- and anti-apoptotic factors. This review article addresses two of them, the pro-apoptotic transcription factor and tumor suppressor protein p53 and its opponent, the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein. The choice of these proteins for special consideration owes to the fact that both of them are key regulators of apoptosis and matter greatly in the pathogenesis of nervous diseases because neurons are not highly proliferative cells. The p53 protein is involved in the regulation of many genes responsible for DNA repair, apoptosis, and other biochemical intracellular processes, which is particularly 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. As has been established, p53 and Bcl-2 closely interact while regulating apoptosis, and their ratio may be an important prognostic factor. This work was aimed to assess the role of these proteins in the pathogenesis of various diseases of the nervous system, and to characterize common dynamic patterns of their expression and coexpression.