DOI: 10.1073/pnas.100049897. Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch

Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch

10.1073/pnas.100049897

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Most of the genetically inherited Alzheimer's disease cases are caused by mutations in the presenilin genes, PS1 and PS2. PS mutations result in the enhanced production of the highly amyloidogenic 42/43 amino acid variant of amyloid β-peptide (Aβ). We have introduced arbitrary mutations at position 286 of PS1, where a naturally occurring PS1 mutation has been described (L286V). Introduction of charged amino acids (L286E or L286R) resulted in an increase of Aβ42/43 production, which reached almost twice the level of the naturally occurring PS1 mutation. Although pathological Aβ production was increased, endoproteolysis of Notch and nuclear transport of its cytoplasmic domain was significantly inhibited. These results demonstrate that the biological function of PS proteins in the endoproteolysis of β-amyloid precursor protein and Notch can be separated.

Bibliography

Kulic, L., Walter, J., Multhaup, G., Teplow, D. B., Baumeister, R., Romig, H., Capell, A., Steiner, H., & Haass, C. (2000). Separation of presenilin function in amyloid Î²-peptide generation and endoproteolysis of Notch. Proceedings of the National Academy of Sciences, 97(11), 5913â5918.

Authors 9

Luka Kulic (first)
Jochen Walter (additional)
Gerd Multhaup (additional)
David B. Teplow (additional)
Ralf Baumeister (additional)
Helmut Romig (additional)
Anja Capell (additional)
Harald Steiner (additional)
Christian Haass (additional)

References 55 Referenced 63

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:38 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:48 p.m.)
Indexed	9 months, 1 week ago (Nov. 19, 2024, 10:41 a.m.)
Issued	25 years, 3 months ago (May 16, 2000)
Published	25 years, 3 months ago (May 16, 2000)
Published Online	25 years, 3 months ago (May 16, 2000)
Published Print	25 years, 3 months ago (May 23, 2000)

Funders 0

None

BibTeX

@article{Kulic_2000, title={Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.100049897}, DOI={10.1073/pnas.100049897}, number={11}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kulic, Luka and Walter, Jochen and Multhaup, Gerd and Teplow, David B. and Baumeister, Ralf and Romig, Helmut and Capell, Anja and Steiner, Harald and Haass, Christian}, year={2000}, month=may, pages={5913–5918} }

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