Speaker: Dr. Carlos W. Bertoncini
Department of Chemistry
University of Cambridge, UK

Thursday, 9 October 2008, 9.30h Aula Fèlix Serratosa

Abstract

The small presynaptic protein α−synuclein is implicated in Parkinson’s disease as this protein forms insoluble amyloid-like deposits which contribute to the loss of dopaminergic neurons in the brain. There is a major need of a detailed information on the structural transitions that occur in the protein under pathological conditions, however, characterization of α-synuclein is technologically challenging as the protein is intrinsically disordered. Furthermore, such lack of stable secondary structure facilitates protein-protein interactions, and increasing evidence suggests that the protein may function as a cellular hub, what scales the complexity of the system by various orders of magnitude.

In the last few years we succeeded in characterizing the ensemble of conformations of α−synuclein by means of NMR spectroscopy and found that intra-molecular long-range interactions are fundamental in maintaining the native state of the protein. In this seminar I will show our latest results towards the characterization of the aggregation pathway of the protein by means of NMR and fluorescence spectroscopy, highlight the potential of small molecule compounds as inhibitors of α- synuclein amyloid formation. In addition, I will provide some examples of protein complexes that modulate the ensemble of conformations and aggregation of α-synuclein, and discuss how this might become another valid target for therapeutic intervention.

• Download poster (PDF)