γ-secretase is an aspartyl protease that controls regulated intramembrane proteolysis of a growing list of single-pass type-I transmembrane proteins, including the amyloid precursor protein (APP) and the Notch-1 receptor. Importantly, γ-secretase is responsible for the final step in the production of amyloid-β peptides (Aβ), the key causative agents of Alzheimer’s disease (AD). Because an age-dependent dysregulation of its specific activity has pointed to the sporadic forms of AD, it remains critical to identify γ-secretase modulators (i) to better understand the biological mechanisms that cause AD, and (ii) for the development of therapies to safely treat this neurodegenerative disorder. We investigated the γ-secretase interactome and identified new endogenous modulators of APP processing and Aβ production. Among these, some play an important role in spatial learning and memory, while changes in their gene expression profiles were found in human brains from neuropathologically-verified AD cases.
Keywords: γ-secretase, intramembrane proteolysis, interactome,
Alzheimer’s disease, learning and memory.
10 maggio
The seminar will be held by Prof. Patrick Fraering of the Campus Biotech Innovation Park & Foundation Eclosion, Geneva, in room C (building CU010) at 12:00.