OXIDATIVE STRESS AS A MOLECULAR BASIS FOR NEURODEGENERATIVE DISEASES AND ANTIOXIDANT THERAPY PATHWAYS
Authors: Mikashinovich Z. , Telesmanich N. , Smirnova O. 
Published: December 2024

The review presents the results of clinical and experimental studies demonstrating the pathogenetic role of oxidative stress in the genesis of neurodegenerative diseases (NDD), obtained using a complex of clinical, laboratory and instrumental methods that reveal the role of oxidative stress and antioxidants in NDD. In the process of preparing the materials, sources from international and domestic databases were used: Scopus, Web of Science, Pub Medline, RSCI, mainly over the past 15 years (2010–2024).
Diseases of the nervous system that differ in etiology and clinical symptoms have common mechanisms associated with damage to biomolecules: improper protein stacking, their aggregation, and violation of the pro- and antioxidant balance. Increased formation of reactive oxygen species (ROS) induces mitoptosis, apoptosis, and ferroptosis, factors that lead to impaired functional activity of neuron structural units as the main element of the nervous system. Given the complexity of the pathogenesis of NDZ, a promising methodological approach is to calculate the leading factors of pathogenesis. Undoubtedly, this makes it possible to standardize diagnosis and therapy, and subsequently create clinical recommendations. The purpose of this work was to analyze the role of participants in oxidative stress in key stages of the inflammatory process underlying NDZ. Despite the fact that there is currently no unambiguous recognition of the effectiveness of antioxidant therapy, nevertheless, the use of antioxidants can be considered as the most important link in neuroprotection, which has a pathogenetic justification.
Metabolic correction in NDH can be divided into 3 groups: natural antioxidants, then endogenous oxidants coming from food, the 3rd group includes drugs of combination therapy and immunotherapy. Mexidol and selenoproteins have antihypoxic and antioxidant effects, which are realized at both the neuronal and vascular levels. Prospects for the development of effective metabolic drugs are associated with the restoration of mitochondrial dysfunction. Synchronization of the metabolic processes underlying the functioning of neuron structures will ensure neurogeneration, slow down neurodegenerative processes and increase life expectancy.
FDA-approved drugs such as acetylcholinesterase inhibitors (donepezil, rivastigmine), as well as levodopa for the treatment of PD, which cross the blood-brain barrier and restore dopamine levels in the substantia nigra, only alleviate symptoms and slow the progression of diseases for several years. New therapeutic approaches aimed at neuroregeneration, i.e. structural and functional restoration of the damaged nervous system through immunomodulation, inhibition of the formation of protein aggregates, disaggregation of improperly folded proteins and induction of autophagy, give hope that the process of degeneration of affected neurons may slow down, and the recovery rate and life expectancy will increase. Due to the complex nature of NDT, a multi-purpose treatment approach is recommended, as it can have additional positive effects.