Abstract
The promiscuous nature of the Alzheimer’s disease associated gamma-secretase (gSec) amongst its substrates remains mysterious after decades of research. In contrast to most other aspartate proteases, gSec cleaves its substrates within the hydrophobic transmembrane domain (TMD), releases an intracellular domain (ICD) and further processes the remaining fragment prior release into the extracellular compartment. Aggregation of the extracellular fragment of the substrate Amyloid Precursor Protein (APP) is related to Alzheimer’s disease.
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