Study of the mechanism of enrichment of APP in endosomes induced by Aβ and its modulation by Gβγ signaling

ANTONINO, MAGDALENA; MARMO, PAULA; LORENZO, ALFREDO; BIGNANTE, ELENA ANAHI

Tegucigalpa

Congreso; 2nd International Symposium LatBrain Initiative.; 2022

LatinBrain

Alzheimer´s disease is characterized by the deposition of aggregated species of amyloid beta (Abeta) in the brain, which leads to progressive cognitive deficits and dementia. We recently found that Abeta assemblies, oligomers and fibrils (o-Abeta and f-Abeta), increase APP and BACE1 interaction in recycling endosomes of human neurons derived from iPSCs by a mechanism dependent of APP/Go/Gbeta-gamma signaling. Now, we are interested on deepen in the APP trafficking in the endo-lysosomal pathway in order to understand the mechanism underlying such effect. We found that Abeta induced an enrichment of APP in recycling endosomes at the expense of a decrement of its levels in lysosomes. This change in APP intracellular distribution is drive by Gbeta-gamma signaling,since is avoided by the pharmacologically inhibitor gallein. Moreover, we found that the changes on APP distribution correlate with an increase in its interaction with BACE1, also modulates by a Gbeta-gamma signaling.