The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Efficient Inhibition of the Alzheimer's Disease β-Secretase by Membrane Targeting
Abstract
β-Secretase plays a critical role in β-amyloid formation and thus provides a therapeutic target for Alzheimer's disease. Inhibitor design has usually focused on active-site binding, neglecting the subcellular localization of active enzyme. We have addressed this issue by synthesizing a membrane-anchored version of a β-secretase transition-state inhibitor by linking it to a sterol moiety. Thus, we targeted the inhibitor to active β-secretase found in endosomes and also reduced the dimensionality of the inhibitor, increasing its local membrane concentration. This inhibitor reduced enzyme activity much more efficiently than did the free inhibitor in cultured cells and in vivo. In addition to effectively targeting β-secretase, this strategy could also be used in designing potent drugs against other membrane protein targets.
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Cites
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Alzheimer’s disease β-amyloid peptides are released in association with exosomes
Rajendran, L., Honsho, M., Zahn, T. R., Keller, P., Geiger, K. D., Verkade, P., & Simons, K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603838103 · Cited by 1,343
Self-citationAβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M. E., Jäggi, F., Wolburg, H., Gengler, S., et al. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400784 · Cited by 986
Structure of the Protease Domain of Memapsin 2 (β-Secretase) Complexed with Inhibitor
Hong, L., Koelsch, G., Lin, X., Wu, S., Terzyan, S., Ghosh, A. K., Zhang, X. C., & Tang, J. (2000) · Science · doi:10.1126/science.290.5489.150 · Cited by 711
100 Years and Counting: Prospects for Defeating Alzheimer's Disease
Roberson, E. D., & Mucke, L. (2006) · Science · doi:10.1126/science.1132813 · Cited by 550
Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases
Nixon, R. A. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.09.018 · Cited by 370
Sorting through the Cell Biology of Alzheimer's Disease: Intracellular Pathways to Pathogenesis
Small, S. A., & Gandy, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.001 · Cited by 324
Lipids as Modulators of Proteolytic Activity of BACE
Kalvodova, L., Kahya, N., Schwille, P., Ehehalt, R., Verkade, P., Drechsel, D., & Simons, K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504484200 · Cited by 289
Self-citationAge-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in Transgenic Drosophila
Greeve, I., Kretzschmar, D., Tschäpe, J.-A., Beyn, A., Brellinger, C., Schweizer, M., Nitsch, R. M., & Reifegerste, R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0283-04.2004 · Cited by 287
Kinoshita, A., Fukumoto, H., Shah, T., Whelan, C. M., Irizarry, M. C., & Hyman, B. T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00643 · Cited by 284
Cited by
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
The secretases: enzymes with therapeutic potential in Alzheimer disease
De Strooper, B., Vassar, R., & Golde, T. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.218 · Cited by 799
Subcellular targeting strategies for drug design and delivery
Rajendran, L., Knölker, H.-J., & Simons, K. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd2897 · Cited by 708
Self-citationThe endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration
Hu, Y.-B., Dammer, E. B., Ren, R.-J., & Wang, G. (2015) · Translational Neurodegeneration · doi:10.1186/s40035-015-0041-1 · Cited by 666
Vassar, R., Kovacs, D. M., Yan, R., & Wong, P. C. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3657-09.2009 · Cited by 577
Metadata
- Authors
- Rajendran, L., Schneider, A., Schlechtingen, G., Weidlich, S., Ries, J., Braxmeier, T., Schwille, P., Schulz, J. B., Schroeder, C., Simons, M., Jennings, G., Knölker, H.-J., & Simons, K.
- Venue
- Science
- Published
- 2008-04-25
- Volume
- 320
- Issue
- 5875
- Pages
- 520-523
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2110747905
- Cited by
- 262
- References
- 24
- FWCI
- 19.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- Rajendran, L., Schneider, A., Schlechtingen, G., Weidlich, S., Ries, J., Braxmeier, T., Schwille, P., Schulz, J. B., Schroeder, C., Simons, M., Jennings, G., Knölker, H.-J., & Simons, K. (2008). Efficient Inhibition of the Alzheimer's Disease β-Secretase by Membrane Targeting. Science. https://doi.org/10.1126/science.1156609
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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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