Research Fellows Directory
Ms Elsa Zacco
King's College London
Protein misfolding is a key early step in the pathology of numerous neurodegenerative disorders, such as Alzheimer's and Parkinson's. The incorrect folding of certain proteins involved in these diseases causes the formation of neurotoxic amyloids that obstruct neuronal communication and lead to cell death. Intervening in this process can be a prophylactic measure for modifying the course of neurodegeneration.
My proposal consists in designing a library of composite molecules to halt amyloid development and promote neuronal communication. To this end, I will based the synthesis of my aggregation inhibitors on the same aromatic amino acids which trigger the self-assembly mechanism of amyloidogenic proteins involved in Alzheimer's and Parkinson's diseases. I will functionalised these amino acid residues for the delivery of antioxidants and carbohydrates, to reduce oxygen radicals responsible for neuronal death and to increase the solubility of the target misfolded protein. The optimal therapeutic molecules for the selected amyloidogenic proteins will be identified in vitro by means of a combination of biochemical and biophysical techniques. I will then study the best candidates also ex vivo on neuronal cells and in vivo in Drosophila, to verify their ameliorating effect against the corresponding disease-associated proteins.
Interests and expertise (Subject groups)