Accumulation of the amyloid-β peptide (Aβ) in senile plaques is an invariable pathological hallmark of Alzheimer´s disease (AD). Aβ is derived by proteolytic processing of the β-amyloid precursor protein (APP) through the combined action of the membrane bound aspartyl proteases β-secretase and γ-secretase. γ-Secretase is a large protein complex composed of the AD-associated presenilin (PS) proteins as catalytic subunit, nicastrin (NCT), APH-1 and PEN-2 and cleaves APP within its transmembrane domain. To allow a better understanding of the mode of action of γ-secretase and of intramembrane proteolysis in general research our group currently focuses on following aspects of γ-secretase biochemistry:

1. Molecular recognition of γ-secretase substrates
2. Modulation of γ-secretase activity