APP-genetic variants uncover potential therapeutic strategies for Alzheimer´s disease.

Congreso; Alexander von Humboldt Kolleg. Current Advances on Neurodegeneration: from Molecular Biology to Translational Medicine.; 2017

Deposition of amyloid-β peptides (Aβ) causes neurodegeneration in Alzheimer's disease (AD). Aβ is generated by regulated proteolysis of the amyloid precursor protein (APP) and pathogenic mutations in APP give rise to early-onset familiar forms of AD (FAD). The dominant hypothesis posits that FAD-APP triggers AD by favoring Aβ aggregation and deposition by multiple mechanisms. However, the direct involvement of APP in the mechanism of neurodegeneration in AD has received much less attention APP is a G protein coupled receptor that signals through Go protein with an evolutionary conserved function. In addition, toxic Aβ assemblies can bind APP and trigger neuronal degeneration. We focused our research on the signaling mechanism elicited by Aβ-APP interaction and found that Go protein signaling plays a significant role in the neurodegenerative mechanism. By studying non-pathogenic APP mutations we identified signaling mechanisms relevant for developing therapeutic strategies for halting neuronal degeneration in AD