The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein
Open accessAbstract
Proteolytic processing of the amyloid precursor protein (APP) by β-secretase, β-site APP cleaving enzyme (BACE1), is the initial step in the production of the amyloid β (Aβ) peptide, which is involved in the pathogenesis of Alzheimer's disease. The normal cellular function of the prion protein (PrP C ), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt–Jakob disease in humans, remains enigmatic. Because both APP and PrP C are subject to proteolytic processing by the same zinc metalloproteases, we tested the involvement of PrP C in the proteolytic processing of APP. Cellular overexpression of PrP C inhibited the β-secretase cleavage of APP and reduced Aβ formation. Conversely, depletion of PrP C in mouse N2a cells by siRNA led to an increase in Aβ peptides secreted into the medium. In the brains of PrP knockout mice and in the brains from two strains of scrapie-infected mice, Aβ levels were significantly increased. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases failed to inhibit the β-secretase cleavage of APP. Using constructs of PrP, we show that this regulatory effect of PrP C on the β-secretase cleavage of APP required the localization of PrP C to cholesterol-rich lipid rafts and was mediated by the N-terminal polybasic region of PrP C via interaction with glycosaminoglycans. In conclusion, this is a mechanism by which the cellular production of the neurotoxic Aβ is regulated by PrP C and may have implications for both Alzheimer's and prion diseases.
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Cites
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A Transmembrane Form of the Prion Protein in Neurodegenerative Disease
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Self-citationTake five—BACE and the γ‐secretase quartet conduct Alzheimer's amyloid β‐peptide generation
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Monoclonal antibodies inhibit prion replication and delay the development of prion disease
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ADAMs family members as amyloid precursor protein α‐secretases
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Cited by
Alzheimer’s disease: Clinical trials and drug development
Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., & Kivipelto, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70119-8 · Cited by 1,217
An overview of APP processing enzymes and products.
Chow, V. W., Mattson, M. P., Wong, P. C., & Gleichmann, M. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8104-z · Cited by 684
Physiology of the prion protein
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Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein
Balducci, C., Beeg, M., Stravalaci, M., Bastone, A., Sclip, A., Biasini, E., Tapella, L., Colombo, L., Manzoni, C., Borsello, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911829107 · Cited by 466
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Gimbel, D. A., Nygaard, H. B., Coffey, E. E., Gunther, E. C., Laurén, J., Gimbel, Z. A., & Strittmatter, S. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0395-10.2010 · Cited by 418
Metadata
- Authors
- Parkin, E. T., Watt, N. T., Hussain, I., Eckman, E. A., Eckman, C. B., Manson, J. C., Baybutt, H. N., Turner, A. J., & Hooper, N. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-06-26
- Volume
- 104
- Issue
- 26
- Pages
- 11062-11067
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2046950900
- Cited by
- 270
- References
- 36
- FWCI
- 17.40
- Type
- journal article
- Language
- en
- Open access
- green
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- Parkin, E. T., Watt, N. T., Hussain, I., Eckman, E. A., Eckman, C. B., Manson, J. C., Baybutt, H. N., Turner, A. J., & Hooper, N. M. (2007). Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0609621104
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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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