IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
artículos
Título:
INSULIN-DEGRADING ENZYME SORTING IN EXOSOMES: A SECRETORY PATHWAY FOR A KEY BRAIN Abeta-DEGRADING PROTEASE
Autor/es:
AYELÉN BULLOJ, MARÍA C. LEAL, HUAXI XU, EDUARDO M. CASTAÑO, AND LAURA MORELLI.
Revista:
Journal of Alzheimer's disease
Referencias:
Año: 2009
ISSN:
1387-2877
Resumen:
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The accumulation of Aβ peptides in the senile plaques is one of the
hallmarks of Alzheimer disease (AD) progression. The endocytic pathway has been
proposed as a major subcellular site for Ab generation while the compartments in which Ab-degrading proteases interact with Ab are still elusive. It was suggested that extracellular Ab degradation may take place by plasma-membrane associated proteases or
by extracellular proteases, among which insulin-degrading enzyme (IDE) is the
most relevant. However, the mechanisms of IDE secretion are poorly understood.
In the present study we used N2a cells to explore if IDE is indeed released through exosomes and the effect of exosomes
release on extracellular levels of Ab. We demonstrated that proteolitically active plasma membrane
associated-IDE is routed in living N2a cells to multivesicular bodies and
subsequently, a major fraction is sorted to exosomes. We described that extracellular
IDE levels decrease if the MVBs generation is interfered and may be positively
modulated by exosomes release under stress-induced conditions. Our results
reinforce the relevance of functional IDE in the catabolism of extracellular Ab.