Mitochondrial and Antioxidant Activity as the Basis of the Neuroprotective Effect of Potential Multitarget Drugs for the Treatment of Neurodegenerative Diseases

BACKGROUND: The mechanisms of neurodegeneration common to many neurodegenerative diseases include oxidative stress, mitochondrial dysfunctions, excitotoxicity, and others. Beyond the broad spectrum of strategies for developing neuroprotective agents that target stagespecific mechanisms in each neurodegenerative disease, considerable attention is also being given to approaches aimed at developing compounds that can effectively modulate general pathogenic mechanisms and enhance the overall resilience of neuronal cells to cell death induction. OBJECTIVE: This review discusses some of the results on new multitarget multipharmacophore agents with neuroprotective effects, particularly through their influence on mitochondrial permeability transition and antioxidant properties. We conducted comprehensive online searches on PubMed to gather the latest data on multitarget multipharmacophore agents consisting of pre-defined pharmacophores that have already demonstrated neuroprotective properties. RESULTS AND DISCUSSION: To create compounds with a desirable spectrum of biological activity, an approach based on the conjugation of specific structural fragments of pharmacologically active substances into a single molecular entity could be used. Core fragments of compounds that have already demonstrated neuroprotective properties due to mitochondrial and antioxidant mechanisms of action can be used as neuroactive scaffolds. CONCLUSION: The combination of several pharmacophores in one molecule may not only result in the mere addition of the useful properties of each component, but may also give rise to new types of biological activity. The examples of the appearance of new properties in such multipharmacophore compounds, not inherent in the reference agents, discussed in our review, may be considered a prospective approach for creating a novel generation of neuroprotective agents.