IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Keeping the balance of amyloid beta with proteases on both sides of the equation.
Autor/es:
CASTAÑO EM; SURACE E; LEAL MC; MORELLI L
Reunión:
Congreso; 46th Reunion Anual. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2010
Resumen:
The progressive accumulation of amyloid â peptides (Aâs), a major feature of the aged human brain, is deeply exacerbated in Alzheimer’s disease (AD), Down syndrome (DS) and hereditary dementias. Regardless of the role of Aâs in the pathogenesis of these diseases, the mechanisms leading to their accumulation are poorly understood. Aâs are released by sequential endoproteolysis of a transmembrane amyloid precursor protein (APP). The aspartyl proteases BACE1 and ã-secretase generate the amino and carboxyl-termini of Aâ peptides, respectively. Within endogenous levels of APP, the activity of BACE1 determines the rate of Aâs generation. After being released, Aâs is purportedly removed by transport to the circulation and in situ proteolysis by Zn2+ metallopeptidases such as insulin-degrading enzyme (IDE) and neprilysin (NEP), among others. In sporadic AD, BACE1 expression and activity are increased while IDE and NEP activities are reduced, consistent with an unbalanced process leading to higher steady-state levels of Aâs. We have recently identified possible subcellular sites of Aâs-IDE interactions and a likely mechanism for IDE non-classical secretion implicated in degradation of extracellular Aâs. Understanding how BACE1 and IDE activities are modulated may provide additional insight into Aâs homeostasis regulation in health and disease.