CoEN 4007- Is prion like propagation of alpha synuclein aggregation associated with a ferroptotic cell death

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This project proposes an innovative study that could rapidly lead to neuroprotective treatmentsagainst Parkinson's disease, a disorder that affects millions of people within our ageing population.Current available drugs attempt to only treat the disease symptoms not its etiology. We base ourproject upon recent findings concerning two main features involved in the targeted death ofspecialized neurons in the brain that secrete a neurotransmitter called dopamine. The first is theabnormal aggregation of a protein called alpha-synuclein that progressively spreads throughout thebrain in correlation with the dopaminergic cell death. The second is the involvement of a newlydiscovered pathway of cell death that we have observed in dopaminergic neurons called ferroptosis.Both phenomena are related with iron; alpha-synuclein is involved in cellular iron balance with itsaggregation state modified by the presence of iron, and ferroptosis is an iron dependent process.Thus this project proposes to elucidate how the modifications to alpha-synuclein observed in Parkinson'sdisease can promote ferroptosis to exacerbate the spreading of neuron death throughout the brain.Outcomes expected from this work are innovative therapeutic strategies based upon recentlygenerated anti-ferroptotic drugs.