Neuroscience Seminar Series,
Friday, February 13, 2015 at 11:30 am
Salle des Conférences (R229), Centre Universitaire des Saints-Pères, 45 rue des Saints-Pères, 75006 Paris
Bart de Strooper, Director of the VIB Center for the Biology of Disease and Professor of Molecular Medicine, KU Leuven
Beta- and Gamma-secretases: fascinating proteases in the membrane and relevant for Alzheimer disease
Over the last decade important progress has been made towards the understanding of the molecular pathobiology of Alzheimer’s Disease. One of the major breakthroughs was the identification of presenilin and its crucial role in the γ-Secretase processing of APP and Notch. We will show in the current presentation that our knowledge on γ-Secretase function and regulation has dramatically progressed in the last years. We will explain how different γ-Secretase complexes have different biological roles, and that selectively targeting them could provide safer drugs. Also increasing insights into structure and function could lead to safer drugs, such as gamma-secretase modulators, but also drugs that specifically interfere with docking of specific substrates to the different γ-Secretases. Finally insight into the regulation of the γ-Secretase complex only starts to emerge, which also could open new opportunities for safer drugs. We will also present unpublished novel insights int o the function of the Beta-secretase or BACE-1, which is now the most favored drug target in Alzheimer disease. It is clear that also this enzyme is involved in important neurobiological phenomena and that the big issue is whether a therapeutic window can be established or not.