IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Plaque-associated over expression of insulin degrading enzyme in the cerebral cortex of aged transgenic Tg2576 mice with Alzheimer pathology.
Autor/es:
MARIA C. LEAL, VERONICA B. DORFMAN, AGATA C. FERNANDEZ GAMBA, BLAS FRANGIONE, THOMAS WISNIEWSKI, EDUARDO M. CASTAñO, EINAR M. SIGURDSSON, LAURA MORELLI
Revista:
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Editorial:
Lippincott Williams and Wilkins
Referencias:
Lugar: Filadelfia; Año: 2006
ISSN:
0022-3069
Resumen:
It was proposed that Insulin-degrading enzyme (IDE) participates in the clearance of amyloid â (Aâ) in the brain and its low expression or activity may be relevant for the progression of Alzheimer`s disease (AD). We performed a longitudinal study of brain level, activity and distribution of IDE in transgenic mice (Tg2576) expressing the Swedish mutation in human Aâ precursor protein. At 16 months of age Tg2576 showed a significant 2-fold increment in IDE protein level as compared to 4.5 and 11 months animals. The peak of IDE was in synchrony with the sharp accumulation of SDS-soluble Aâ and massive Aâ deposition into plaques. At this stage, IDE appeared surrounding Aâ fibrillar deposits within GFAPpositive astrocytes suggesting that it was locally over-expressed during Aâ-mediated inflammation process. When primary astrocytes were exposed to fibrillar Aâ in vitro, IDE protein level increased as compared to control and this effect was reduced by the addition of U0126, a specific inhibitors of the ERK1/2 Mitogen-Activated Protein Kinase (MAPK) cascade. We propose that in Tg2576 mice and in contrast to its behavior in AD brains, active IDE increases with age around plaques as a component ofastrocyte activation due to Aâ triggered inflammation.â (Aâ) in the brain and its low expression or activity may be relevant for the progression of Alzheimer`s disease (AD). We performed a longitudinal study of brain level, activity and distribution of IDE in transgenic mice (Tg2576) expressing the Swedish mutation in human Aâ precursor protein. At 16 months of age Tg2576 showed a significant 2-fold increment in IDE protein level as compared to 4.5 and 11 months animals. The peak of IDE was in synchrony with the sharp accumulation of SDS-soluble Aâ and massive Aâ deposition into plaques. At this stage, IDE appeared surrounding Aâ fibrillar deposits within GFAPpositive astrocytes suggesting that it was locally over-expressed during Aâ-mediated inflammation process. When primary astrocytes were exposed to fibrillar Aâ in vitro, IDE protein level increased as compared to control and this effect was reduced by the addition of U0126, a specific inhibitors of the ERK1/2 Mitogen-Activated Protein Kinase (MAPK) cascade. We propose that in Tg2576 mice and in contrast to its behavior in AD brains, active IDE increases with age around plaques as a component ofastrocyte activation due to Aâ triggered inflammation.