Throughout their life cycles, cells are subject to a variety of stresses that lead to a compromise between cell death and survival. Survival is partially provided by the cell proteostasis network, which consists of molecular chaperones, a ubiquitin-proteasome system of degradation and autophagy. The cooperation of these systems impacts the correct function of protein synthesis/modification/transport machinery starting from the adaption of nascent polypeptides to cellular overcrowding until the utilization of damaged or needless proteins. Eventually, aging cells, in parallel to the accumulation of flawed proteins, gradually lose their proteostasis mechanisms, and this loss leads to the degeneration of large cellular masses and to number of age-associated pathologies and ultimately death. In this review, we describe the function of proteostasis mechanisms with an emphasis on the possible associations between them.

Many serious illnesses, including diabetes, obesity, osteoporosis, and neurodegenerative diseases, are caused by chronic inflammation that develops in fat tissue, bones, or the brain. This inflammation occurs due to a shift in macrophage (microglia) polarization toward a proinflammatory M1 phenotype. It has now been proven that macrophage polarization is determined by the intracellular level of autophagy in the macrophage. By modulating autophagy, it is possible to cause a switch in macrophage activity towards M1 or M2. Summarizing the material accumulated in the literature, we believe that activation of autophagy reprograms the macrophage towards M2, replacing its protein content and receptor apparatus, and activate a another type of metabolism. The term “reprogramming” is most appropriate for this process, since it is followed by a change in the functional activity of the macrophage, namely a switch from cytotoxic proinflammatory activity to anti-inflammatory (regenerative) activity. Modulation of autophagy may be an approach to the treatment of cancer, neurodegenerative disorders, osteoporosis, diabetes and other serious diseases.

Chemotherapy and radiotherapy are a colossal stress factor for tumor cells. In response to therapy, the entire evolutionarily fixed response of cells to stress is activated. This happens at all levels of cell organization, namely at the protein level and the DNA level. This response involves the cell proteostasis system, DNA repair systems, tumor suppressor genes, and many other cell systems. We will consider the role of the main systems of proteostasis in these processes, namely, macroautophagy and chaperones, which are part of the integrated response of the cell to stress. As a result of the cell’s response to stress, the tumor cell becomes even less differentiated, activating the genes and intracellular systems necessary for survival. Cells that have responded to stress in this way have a more aggressive phenotype that is significantly more resistant to therapy. Under the influence of stress, the cell evolutionarily simplifies, which gives it additional chances for survival. On the one hand, autophagy contributes to a decrease in tumor cell differentiation and its plasticity, and on the other hand, it maintains a certain stability, being responsible for the integrity of the genome and freeing the cell from damaged organelles and defective proteins. Both autophagy and chaperones contribute to the acquisition of multidrug resistance by the tumor, which further complicates therapy. Understanding these processes makes it possible to develop new therapeutic approaches, taking into account the multistage nature of carcinogenesis.

Chemotherapy and radiotherapy are colossal stress factors for tumor cells. In response to therapy, the entire evolutionarily fixed response of cells to stress is activated. This happens at all levels of cell organization, namely, at the protein level and the DNA level. This response includes the cell proteostasis system, DNA-repair systems, tumor-suppressor genes, and many other cell systems. We will consider the role of the main systems of proteostasis in these processes, namely, macroautophagy and chaperones, which are parts of the integrated cell response to stress. As a result of the cell’s response to stress, the tumor cell becomes even less differentiated, activating the genes and intracellular systems necessary for survival. Cells that have responded to stress in this way have a more aggressive phenotype that is significantly more resistant to therapy. Under the influence of stress, the cell evolutionarily simplifies, which gives it additional chances for survival. Autophagy, on one hand, contributes to a decrease in tumor-cell differentiation and its plasticity, and, on the other hand, it maintains a certain stability, being responsible for the integrity of the genome and freeing the cell from damaged organelles and defective proteins. Both autophagy and chaperones contribute to the acquisition of multidrug resistance by the tumor, which further complicates therapy. Understanding these processes, taking into account the multistage nature of carcinogenesis, makes it possible to develop new therapeutic approaches.

The role of JNK1,2 stress kinases in the regulation of premature senescence stimulated by sodium butyrate (NaB), a histone deacetylase inhibitor, has been studied. It was found that NaB did not block...