Study of the role of oxidative stress in the onset of neurodegenerative diseases

The model cell system that we use in our laboratory is primary and/or transformed fibroblasts from patients with Cockayne syndrome, a rare disease characterized by a neurodegenerative phenotype and premature aging. We have shown that Cockayne syndrome fibroblasts present mitochondrial dysfunction with membrane depolarization and alteration of mitochondrial morphology, alterations in the mitophagic process and increase in ROS with consequent increase in oxidative damage to nuclear DNA. By over-expressing Parkin (mitophagy protein) or by inhibiting Drp1 (mitochondrial fission protein) we were able to reverse the dysfunctional mitochondrial phenotype.
Mitochondrial dysfunction characterizes various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, therefore we aim to characterize, in different cell types, mitochondrial dysfunction by analyzing gene and protein expression, as well as post-translational modifications of proteins involved in the mitochondrial dynamics process.
Furthermore, in order to broaden the range of biomarkers that can be used in future population studies, we are developing quantitative amplification techniques to analyze both nuclear and mitochondrial DNA damage, measuring deletions and oxidized guanine levels.
Our aim is therefore, through an integrated approach, to further characterize the alterations at the mechanistic level underlying neurodegenerative diseases and to identify potential new biomarkers, both predictive and therapeutic.