INTERACTIONS OF METAL IONS AND METAL-BASED COMPOUNDS WITH ALPHA-SYNUCLEIN: FROM BASIC RESEARCH TO THERAPY

CLAUDIO O. FERNANDEZ

Barcelona

Conferencia; 11th International Symposium on Applied Bioinorganic Chemistry (ISABC2011); 2011

The aggregation of alpha-synuclein (AS) is a critical step in the etiology of Parkinson?s disease (PD). Protein-metal interactions play an important role in AS aggregation and might represent the link between the pathological processes of protein aggregation, oxidative damage and neuronal cell loss. Our studies revealed a hierarchal effect of metal interactions on AS aggregation kinetics, dictated by structural factors corresponding to different protein domains [1-3]. These results constituted the basis to investigate the impact of metal ion occupancy on the binding and inhibitory capacity of anti-amyloidogenic small molecules [4,5]. The elucidation of molecular and structural determinants of these  interactions serves as scaffold for on going structure-based drug discovery efforts targeting AS amyloid formation.