Cellular Mechanisms of Damage and Compensation in the Brain in Cerebral Ischemia: Molecular Proteostasis Control Systems as a Target for Therapy

The relevance of the work is due to the wide spread of cerebrovascular pathology and ischemic strokes among the population. Most studies are devoted to the study of early brain damage in cerebral ischemia, while insufficient attention has been paid to the mechanisms of adaptation and long-term brain disorders. At the same time, delayed death of nerve cells in ischemia is not a predetermined and irreversible process, leaving opportunities for therapeutic intervention. There is a need to search for new data on the molecular and cellular mechanisms of damage development and compensatory processes in brain neurons in the dynamics of cerebral ischemia of varying severity. At the same time, the activation of compensatory mechanisms will reduce the severity of neurodegenerative disorders in the brain, increase the effectiveness of the treatment. An important role in the development of neurodegeneration is played by protein aggregates, which can be localized in nerve cells, in the intercellular space and cerebrospinal fluid. They are formed on the basis of damaged proteins, the violation of the structure of which can be caused by hypoxic and nitrosative stress, inflammatory processes provoked by ischemia, death of neurons. Therefore, an important role in preventing the development of secondary brain damage after ischemia can be played by cellular systems responsible for protein homeostasis, the protein synthesis apparatus, chaperones, the system of autophagy and elimination of damaged proteins ((ubiquitin, proteasome), as well as energy-intensive adaptation processes.