The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Presenilin and nicastrin regulate each other and determine amyloid β-peptide production via complex formation
Open accessAbstract
Amyloid β-peptide (Aβ) is generated by the consecutive cuts of two membrane-bound proteases. β-Secretase cuts at the N terminus of the Aβ domain, whereas γ-secretase mediates the C-terminal cut. Recent evidence suggests that the presenilin (PS) proteins, PS1 and PS2, may be γ-secretases. Because PSs principally exist as high molecular weight protein complexes, biologically active γ-secretases likely require other cofactors such as nicastrin (Nct) for their activities. Here we show that preferentially mature Nct forms a stable complex with PSs. Furthermore, we have down-regulated Nct levels by using a highly specific and efficient RNA interference approach. Very similar to a loss of PS function, down-regulation of Nct levels leads to a massive accumulation of the C-terminal fragments of the β-amyloid precursor protein. In addition, Aβ production was markedly reduced. Strikingly, down-regulation of Nct destabilized PS and strongly lowered levels of the high molecular weight PS1 complex. Interestingly, absence of the PS1 complex in PS1 −/− cells was associated with a strong down-regulation of the levels of mature Nct, suggesting that binding to PS is required for trafficking of Nct through the secretory pathway. Based on these findings we conclude that Nct and PS regulate each other and determine γ-secretase function via complex formation.
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Self-citationIntracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42
Wild-Bode, C., Yamazaki, T., Capell, A., Leimer, U., Steiner, H., Ihara, Y., & Haass, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16085 · Cited by 303
Self-citationWolfe, M. S., Xia, W., Moore, C. L., Leatherwood, D. D., Ostaszewski, B., Rahmati, T., Donkor, I. O., & Selkoe, D. J. (1999) · Biochemistry · doi:10.1021/bi982562p · Cited by 289
Cited by
Jankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075
Self-citationAph-1, Pen-2, and Nicastrin with Presenilin Generate an Active γ-Secretase Complex
De Strooper, B. (2003) · Neuron · doi:10.1016/s0896-6273(03)00205-8 · Cited by 965
Liao, Y.-F., Wang, B.-J., Cheng, H.-T., Kuo, L.-H., & Wolfe, M. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402034200 · Cited by 389
Ling, Y., Morgan, K., & Kalsheker, N. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(03)00133-x · Cited by 224
Metadata
- Authors
- Edbauer, D., Winkler, E., Haass, C., & Steiner, H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-06-04
- Volume
- 99
- Issue
- 13
- Pages
- 8666-8671
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2167959613
- Cited by
- 225
- References
- 6
- FWCI
- 19.29
- Type
- journal article
- Language
- en
- Open access
- green
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- Edbauer, D., Winkler, E., Haass, C., & Steiner, H. (2002). Presenilin and nicastrin regulate each other and determine amyloid β-peptide production via complex formation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.132277899
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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