Mechanism for restoring brain cells from damaged proteins has been discovered

The aging process of the central nervous system is characterized by a progressive decrease in the efficiency of biological processes in neurons. One of the key factors in this decline is a violation of protein quality control, which ensures timely processing and utilization of cellular components. An international team of researchers from Germany and Italy analyzed how oxidative stress caused by an excess of reactive oxygen species affects the molecular control systems inside cells.

The work focuses on deubiquitylases (DUBs), specialized enzymes that remove ubiquitin tags from protein molecules. The process is a critical step in regulating the life cycle of proteins. In a study published in Nature Communications, it was found that the activity of these enzymes decreases significantly in the aging brain. Interestingly, the total number of enzyme molecules in the tissues remains unchanged, but their functionality is limited due to the chemical modification of cysteine residues. These changes act as a physiological regulator of the rate of enzymatic reactions, leading to the accumulation of unprocessed proteins and disrupting cellular homeostasis.

The most significant discovery was the confirmation of the reversibility of this process. In a series of experiments, it was demonstrated that the functional inhibition of deubiquitases can be reversed by the antioxidant compound NACET (N-acetylcysteine ethyl ester). This compound acts as a precursor for the amino acid cysteine and promotes the synthesis of glutathione, a key component of the body’s antioxidant defense system. When exposed to NACET, the enzymes regained their catalytic activity. This suggests that the age-related changes in this case are not due to irreversible protein degradation but rather to dynamic alterations in the chemical environment within the cell.

The identified mechanism is essential for understanding the etiology of neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, in which protein degradation plays a fundamental role. The identification of deubiquitases as an early target of age-related changes opens up new avenues for developing therapeutic interventions. Further research is needed to determine the long-term effects of restoring enzymatic activity on cognitive functions such as memory and learning. The results obtained in laboratory mouse and fish models provide a scientific basis for subsequent verification of these mechanisms in humans.