Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

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Biochemistry of gamma-secretase

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Intramembrane proteolysis of APP by the γ-secretase complex

Intramembrane proteolysis of APP by the γ-secretase complex.

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 in our group currently focuses on following aspects of γ-secretase biochemistry:

  • Structure/function analysis of γ-secretase subunits PS, NCT, APH-1 and PEN-2
  • Molecular recognition of γ-secretase substrates
  • Modulation of γ-secretase activity
  • Lipid dependence of γ-secretase activity

Responsible for content: Prof. Dr. Harald Steiner; Prof. Dr. Dr. h.c. Christian Haass