Amyloid toxicity and neuronal degeneration.

ALFREDO LORENZO

Carlos Paz

Simposio; Alexander Von Humboldt Kolleg - Current Advances on Neurodegeneration: from Molecular Biology to Translational Medicine; 2017

Alexander Von Humboldt Kolleg

Deposition of amyloid-β peptides (Aβ) causesneurodegeneration in Alzheimer?s disease (AD). Aβ is generated by regulatedproteolysis of the amyloid precursor protein (APP) and pathogenic mutations inAPP give rise to early-onset familiar forms of AD (FAD). The dominanthypothesis posits that FAD-APP triggers AD by favoring Aβ aggregation and depositionby multiple mechanisms. However, the direct involvement of APP in the mechanismof neurodegeneration in AD has received much less attention.              APP is a G protein coupled receptorthat signals through Go protein with an evolutionary conserved function. Inaddition, toxic Aβ assemblies can bind APP and trigger neuronal degeneration. Wefocused our research on the signaling mechanism elicited by Aβ-APP interactionand found that Go protein signaling plays a significant role in theneurodegenerative mechanism. By studying non-pathogenic APP mutations we identifiedsignaling mechanisms relevant for developing therapeutic strategies for haltingneuronal degeneration in AD.