IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Metal ions in brain diseases: Bioinorganic Chemistry and Therapy.
Autor/es:
FERNANDEZ, C.O.
Lugar:
Lanzarote
Reunión:
Conferencia; Bioinorganic Chemistry Zing Conference; 2013
Resumen:
Alpha-synuclein (AS) aggregation is associated to neurodegeneration in Parkinson´s disease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS-metal interactions and their effect on AS aggregation constitutes a key step towards understanding the role of metal ions in AS amyloid formation and neurodegeneration. This presentation provides a comprehensive view of recent advances made by our group in the bioinorganic chemistry of AS amyloid diseases [1-4]. A hierarchy in AS-metal ion interactions has been established: while divalent metal ions interact at a non-specific, low-affinity binding interface at the C-terminus of AS, copper binds with high affinity at the N-terminal region and it is the most effective metal ion in accelerating AS filament assembly. The strong link between metal binding specificity and its impact on aggregation will be discussed on a mechanistic basis. A detailed description of the structural features and coordination environments of copper to AS will be presented and discussed in the context of oxidative cellular events that might lead to the development of PD. Overall, our research findings support the notion that perturbations in copper metabolism may be a common upstream event in the pathogenesis of neurodegenerative processes.