ROLE OF APP/GO PROTEIN Gbeta-gamma COMPLEX SIGNALING ON Amyloid Beta NEURODEGENERATION IN ALZHEIMER´S DISEASE MODELS.

BIGNANTE, ELENA ANAHI; PONCE, NICOLÁS ERIC; FLORENCIA HEREDIA; MUSSO, JULIANA; KRAWCZYK, MARÍA C.; MILLAN J; BOCCIA, MARIANO M.; ALFREDO LORENZO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC

Deposition of amyloid-beta peptides (Abeta) causes neurodegeneration in Alzheimer?s disease (AD). Abeta is generated by regulated proteolysis of the amyloid precursor protein (APP). However, the involvement of APP, beyond its role as source of Abeta, in the mechanism of Abeta-induced degeneration remains elusive. Methods. FRET and co-immunoprecipitation were performed in primary hippocampal cultures and HEK293T in order to identify the effect of Abeta on APP and Go interaction. The physiopathological relevance of APP and Go signaling in Abeta neurodegeneration was determined by analyzing neuronal dystrophy, tau phosphorylation and neuronal death in primary hippocampal cultures and by assessment of memory performance in the 3xTgAD mice using the novel object recognition (NOR) test. Results. We found that toxic Abeta assemblies enhance APP and Go interaction (p < 0.001). APP overexpression renders hippocampal neurons vulnerable to Abeta-toxicity by a mechanism that requires Go-Gbeta-gamma signaling and p38-MAPK activation (p