IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Misfolding and aggregation in Alzheimers 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:
Alzheimers 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