INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ASTROGLIAL METABOTROPIC GLUTAMATE RECEPTOR 3 INDUCES THE NON-AMYLOIDOGENIC PATHWAY BY MODULATING ALPHA AND BETA SECRETASE EXPRESSION
Autor/es:
DANIELA DURAND; LILA CARNIGLIA; CARLA CARUSO; MERCEDES LASAGA
Lugar:
New Orleans
Reunión:
Congreso; 42nd Annual Meeting of the Society for Neuroscience; 2012
Institución organizadora:
Society for Neuroscience
Resumen:
Alzheimer’s disease is characterized by the presence of amyloid β (Aβ) plaques in the brain. Aβ derives from proteolytic cleavage of amyloid precursor protein (APP) by - (BACE) and γ-secretases. On the other hand, α-secretase cleaves APP within the Aβ domain generating a soluble fragment (sAPPα) which shows neuroprotective effects and improves memory. ADAM-10 and ADAM-17 metalloproteases have been identified as the main α-secretases expressed in the brain. Group II metabotropic glutamate receptors (mGluR) include mGlu3R and mGlu2R, being mGlu3R expressed in astrocytes. Astroglial mGlu3R activation reduces neuronal degeneration induced by Aβ in vitro. Although it has been shown that a non-selective agonist of mGluR promotes the non-amyloidogenic pathway in astrocytes, most likely by activating group II mGluR, this issue has not been further explored. Therefore, we studied the involvement of mGlu3R in the non-amyloidogenic shedding of APP in primary cultured rat astrocytes. The mGlu3R-selective agonist LY379268 increased sAPPα release from astrocytes in a dose-dependent manner (LY0.01 µM p