IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Targeting the fibrillation pathway of Alpha-Synuclein: A therapeutic approach to Parkinson´s disease
Autor/es:
LAMBERTO, G. R.; BINOLFI, A.; ORCELLET, M. L.; BERTONCINI, C. W.; ZWECKSTETTER, M.; GRIESINGER, C.; FERNÁNDEZ, C.O.
Lugar:
Ciudad de México, México
Reunión:
Workshop; USA-Mexico Workshop in Biological Chemistry: Multidisciplinary Approaches to Protein Folding; 2009
Institución organizadora:
Centro de Investigación y de Estudios Avanzados (Cinvestav)
Resumen:
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The misfolding of proteins into a toxic
conformation is proposed to be at the molecular foundation of neurodegenerative
disorders including Creutzfeldt-Jacob disease, Alzheimer disease and
Parkinson´s disease (PD). Neurodegeneration in PD is progressive and
characterized by the loss of dopaminergic neurons in the substantia nigra and
the presence of fibrillar cytoplasmatic aggregates of alpha-synuclein (AS) in
multiple brain regions. Currently, no preventative therapy is available for PD
and related synucleinopathies. Identification of therapeutic drugs is not only
complicated by a lack of understanding of many of the key aspects of PD pathogenesis
but also by the multifactorial etiology of the disease. The aggregation pathway
of AS represents then one obvious target for therapeutic intervention in PD.
Indeed, one approach to the development of therapeutic agents in
neurodegenerative diseases has been the use of small molecules that
specifically and efficiently inhibit the aggregation process. In this work we
report high-resolution structural information of the interaction between AS and
some of the most studied aggregation inhibitors. The elucidation of the
structural details of the interactions provided the basis for understanding the
role of specific residues in the fibrillation pathway of AS and shed new light
into the mechanistic basis that direct the inhibitory process of anti-amyloidogenic
compounds.