Molecular Neurobiology Department seminar

Speaker: professor Andrey Abramov, Institute of Neurology, University College London (UK)

Presentation title: Mitochondria, calcium and reactive oxygen species in the mechanism of neurodegeneration in Parkinson's disease

Author's abstract:

Parkinson’s disease is a common neurodegenerative disease characterised by the progressive loss of dopaminergic and non-dopaminergic neurons, and the accumulation of intracellular inclusions containing aggregated α-synuclein. The majority of PD is sporadic (>90%) but approximately 5-10% of cases are familial and due to mutations in PD-related genes, principally α-synuclein, parkin, PINK1, DJ-1, and LRRK2. Abnormally aggregated α-synuclein is found in all cases of sporadic PD. Strong evidence exists to support a role of oxidative stress in the pathogenesis of many neurodegenerative diseases, including PD. Antioxidant therapy is proven to be effective PD in experiments on cellular level, but most of the clinical trials failed to have any protection on the patient level. Considering this, the identification of ROS producers and targets of oxidative stress is important for finding the mechanisms of disease prevention.

We found that oligomeric α-synuclein induced ROS production and that it was independent of all known cellular enzymatic sources but depended on the presence of heavy metal ions. In familial form of PD, such a PINK1 mutation or deficiency, activation of NADPH oxidase induces oxidative stress responsible for deregulation of energy metabolism. Importantly, dopamine signalling activates monoamine oxidase (MAO) and induces further oxidation. Our findings further support the importance of oxidative damage in familial and sporadic forms of Parkinson’s disease.

Chair: Alexey Semyanov; E-mail: semyanov@ibch.ru

march 2, 2018