Metabotropic glutamate receptor 3-sAPPα: novel pathway in class-A scavenger receptor-mediated β-Amyloid clearance by astrocytes

D. DURAND; J. TURATI; L. CARNIGLIA; D. RAMIREZ; J. SABA; C. CARUSO; R. VON BERNHARDI; M. LASAGA

CABA

Congreso; Reunión conjunta de Sociedades de Biociencias, 13-17/11/2017, Buenos Aires, Argentina.; 2017

SAIC

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