Artificial enzymes for oxidative stress
Cardiovascular diseases are still the number one cause of death and neurodegenerative disorders are becoming a major global health burden particularly with the ageing of the population. Oxidative stress, originating from an imbalance between the generation of reactive oxygen species and the antioxidant defence mechanisms of cells, has been implicated in these diseases and evidence shows that a common denominator are superoxide radicals. Given the prevalence of these diseases among the European population, the EU-funded 'Designing metallopeptides for the removal of superoxide radicals' (MFROSPEP) project aimed to find new therapeutic solutions. Researchers therefore decided to mimic the natural processes that take place within cells to fight against the detrimental effects of oxidative stress conditions. Cells possess superoxide dismutases (SODs), endogenous metalloenzymes that convert superoxide radicals into the less toxic dioxygen and hydrogen peroxide. The MFROSPEP project aimed to replicate this process, known as dismutation, by developing novel and better antioxidant compounds. In this context, they formulated promising peptide scaffolds capable of binding redox active metal ions under physiological conditions. Their degrees of flexibility allowed the metal ion redox cycling needed for the catalytic removal of superoxide radicals and therefore, these metallopeptide systems showed potential to evolve as SOD mimics. Overall, the MFROSPEP research increased our understanding of the key factors needed to develop antioxidant agents. The generated peptide systems will form the basis for the development of artificial SOD enzymes for therapeutic applications against cardiovascular and neurodegenerative disorders. Considering the economic health burden associated with neurodegeneration, implementation of the MFROSPEP deliverables could ameliorate part of the disease phenotype.
Keywords
Antioxidant, reactive oxygen species, cardiovascular disease, neurodegenerative disorders, superoxide dismutase, artificial enzyme, metallopeptides
