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Presenilins and the intramembrane proteolysis of proteins: facts and fiction

Nature Cell Biology volume 3, pages E221–E225 (2001)Cite this article

Missense mutations in the genes coding for presenilin 1 and presenilin 2 cause familial Alzheimer's disease — a progressive neurodegenerative disorder of the central nervous system. Loss-of-function mutations of these genes in Drosophila, Caenorhabditis elegans and mice cause severe lethal phenotypes, which implicates the presenilins genetically in the Notch signalling pathway. The hypothesis that presenilins are aspartyl proteases that cleave the amyloid precursor protein and Notch can explain the phenotypes. Direct evidence for this hypothesis is, however, difficult to obtain. Moreover, presenilin 1 is a multifunctional protein, as exemplified by its role in the Wnt/β-catenin signalling pathway.

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Figure 1: PS regulated intramembrane proteolysis of Notch and APP.
Figure 2: Regulated intramembrane proteolysis and vesicular trafficking of SREBP/SCAP.
Figure 3: APP trafficking and proteolytic processing.

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Acknowledgements

We thank the many researchers who provided information before publication and all members of our laboratory for their intellectual input. We acknowledge the financial support of the Bayer Research Network, the Flanders Interuniversity Institute for Biotechnology, The Human Frontier of Science Program, the National Fund for Scientific Research–Flanders and the Katholieke Universiteit Leuven.

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  1. Center for Human Genetics, Neuronal Cell Biology Laboratory, The K.U. Leuven and Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, 3000, Belgium

    Bart De Strooper & Wim Annaert

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Correspondence to Bart De Strooper.

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Strooper, B., Annaert, W. Presenilins and the intramembrane proteolysis of proteins: facts and fiction. Nat Cell Biol 3, E221–E225 (2001). https://doi.org/10.1038/ncb1001-e221

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