Metabotropic glutamate receptor 3 - sAPP alpha: novel pathway in class-A scavenger receptor-mediated beta-Amyloid clearance by astrocytes

DANIELA DURAND; DELIA RAMÍREZ; ROMMY VON BERNHARDI; LILA CARNIGLIA; CARLA CARUSO; JUAN TURATI; JULIETA SABA; MERCEDES LASAGA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Among metabotropic glutamate receptors (mGluR), astroglial mGlu3R subtype has particularly shown a broad range of neuroprotective functions. Our previous results demonstrated that mGlu3R activation by the synthetic agonist LY379268 promotes non-amyloidogenic APP cleavage, thereby releasing sAPPα neuroprotective fragment from astrocytes. Moreover, sAPPα mediates the antiapoptotic effect of conditioned medium from LY379268-treated astrocytes (LY-ACM) against Aβ toxicity in hippocampal neurons. We also showed that LY379268 increases Aβ uptake by astrocytes, which parallels the reduction in co-cultured neuron death. In order to elucidate the mechanism involved in Aβ uptake by astrocytes, the present study shows that LY-ACM increased HiLyte Fluor-Aβ25-35 uptake by naïve astrocytes (p