Structure and function of gamma-secretase.
The gamma-secretase complex is a prime target for pharmacological intervention in Alzheimer's disease and so far drug discovery efforts have yielded a large variety of potent and rather specific inhibitors of this enzymatic activity. However, as gamma-secretase is able to cleave a wide variety of physiological important substrates, the real challenge is to develop substrate-specific compounds. Therefore, obtaining structural information about gamma-secretase is indispensable. As crystal structures of the complex will be difficult to achieve, applied biochemical approaches need to be integrated with structural information obtained from other intramembrane-cleaving proteases. Here we review current knowledge about the structure and function of gamma-secretase and discuss the value of these findings for the mechanistic understanding of this unusual protease.
Tolia
Alexandra
A
Center for Human Genetics, KULeuven and Department for Developmental and Molecular Genetics, VIB, Herestraat 49, 3000 Leuven, Belgium.
De Strooper
Bart
B
D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D015398:Signal Transduction
D053829:Amyloid Precursor Protein Secretases