Cell death accelerated by hereditary dystrophin mutations is a major cause of heart failure and
premature death in patients. In the search for new therapeutic approaches, we found that
upregulation of NOS worsens the phenotype of dystrophin-deficient human pluripotent stem
cells. At the same time, the close link between dystrophin, the dystrophin-glycoprotein complex
and circadian clockwork was shown. In this project, we aim to test whether the activity of
circadian synchronizer melatonin can alter the progression of the phenotype of the hiPSC
model of Duchenne dystrophy. We also aim to exploit melatonin as an antioxidant that
upregulates protective enzymes of redox metabolism and scavenges reactive oxygen species
and to test the direct protective effect of melatonin on our cell models in standard media and in
high glucose environment. The project includes the assessment of melatonin production by the
cells. This project combines the applicant's long-standing interest in the circadian rhythms and
melatonin with the co-applicant's unique cardiomyocytes hiPSC model.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.