IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Misfolding and aggregation in Alzheimer’s disease: Targeting the beta-amyloid
Autor/es:
ARIEL ALEJANDRO VALIENTE GABIOUD; ANDRES BINOLFI; CLAUDIO O. FERNANDEZ
Reunión:
Congreso; XXXIX Annual Meeting of Argentinean Biophysical Society SAB 2010, workshop CeBEM, structural biology in Latin America, 3rd Latin American Protein Society Meeting; 2010
Resumen:
Alzheimer’s disease is the most common neurodegenerative disorder and represents one of the leading causes of death in the developed world. The major neuropathological changes in the brains of AD patients are neuronal death, particularly in regions related to memory and cognition, and the presence of intra- and extracellular abnormal protein aggregates, known as neurofibrillary tangles and amyloid plaques, respectively. Extracellular amyloid deposits have revealed to be essentially composed of a hydrophobic 40-43 amino acid peptide called B-amyloid peptide. AB misfolding and aggregation are probably the first pathological processes in AD. The pathogenic role of AB in AD has been supported by the discovery of several mutations in AB tightly linked to inherited forms of the disease. Evidence that AB plays a causative role in AD pathology has also come from several model systems. AB is toxic to neurons in culture, and plaque formation in the brians of transgenic animals overexpressing human AB peptide also leads to neuronal toxicity. These evidences and the abundant knowledge accumulated about the molecular mechanism of amyloid formation make the inhibition of AB misfolding and oligomerization an attractive therapeutic target for AD. As a consequence, much of the work on AB in the last years has focused on the development of amyloid inhibitors. However, the usefulness of most of the studied compounds as amyloid inhibitors was comprised by the unknown structural and mechanistic basis of their inhibitory effects. In this work, we characterized structurally the interaction between AB and one of the most potent amyloid inhibitors. The structural basis for the anti-amyloid