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Restricted Location of PSEN2/γ-Secretase Determines Substrate Specificity and Generates an Intracellular Aβ Pool
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The PS1-containing γ-secretase complex is widely distributed in the cell, whereas a single acidic-dileucine sorting motif in PS2 directs the complex to late endosomes/lysosomes.
“While the complex containing PS1 is widely distributed in the cell, a single acidic-dileucine sorting motif present in PS2 directs the γ-secretase complex to late endosomes/lysosomes (Sannerud et al., 2016).”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Sannerud et al., 2016
The subcellular location and substrate specificity of γ-secretase may vary depending on the presence of PS1 or PS2 in the complex.
“The subcellular location and substrate specificity of γ-secretase may vary depending on the presence of PS1 or PS2 in the complex.”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Sannerud et al., 2016
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The FoldX web server: an online force field
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“Molecular Modeling The structure of the AP1 core (PDBID: 4P6Z) was used as template for modelling binding with the PSEN2 peptide motif VCDERTSLMS using FoldX force field (Schymkowitz et al., 2005).”
Self-citationKuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.211 · Cited by 532
Self-citationAmyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide
Hu, X., Crick, S. L., Bu, G., Frieden, C., Pappu, R. V., & Lee, J.-M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911281106 · Cited by 426 · cited 3×
“…local concentrations of Aβ in these organelles, together with an acidic pH has profound effects on the conformation, aggregation and probably toxicity of Aβ (Esbjorner et al., 2014; Hu et al., 2009) which may be further accelerated by relative increases in more toxic Aβ42 (Kuperstein et al., 2010).”
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372
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Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity
Friedrich, R. P., Tepper, K., Rönicke, R., Soom, M., Westermann, M., Reymann, K., Kaether, C., & Fändrich, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904532106 · Cited by 303 · cited 1×
“In addition, we find that PSEN2 produces a distinct intracellular pool of Aβ that has been inferred to be pathological relevant, but whose origin was never precisely determined (Friedrich et al., 2010; Gouras et al., 2010; Pensalfini et al., 2014).”
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Metadata
- Authors
- Sannerud, R., Esselens, C., Ejsmont, P., Mattera, R., Rochin, L., Tharkeshwar, A. K., De Baets, G., De Wever, V., Habets, R., Baert, V., Vermeire, W., Michiels, C., Groot, A. J., Wouters, R., Dillen, K., Vints, K., Baatsen, P., Munck, S., Derua, R., Waelkens, E., Basi, G. S., Mercken, M., Vooijs, M., Bollen, M., Schymkowitz, J., Rousseau, F., Bonifacino, J. S., Van Niel, G., De Strooper, B., & Annaert, W.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 166
- Issue
- 1
- Pages
- 193-208
- ISSN
- 0092-8674
- PMC
- PMC7439524
- Cited by
- 299
- References
- 6
- Language
- en
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