The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Inhibition of γ‐secretase causes increased secretion of amyloid precursor protein C‐terminal fragments in association with exosomes
Abstract
Alzheimer's disease (AD) is the most common form of dementia and is associated with the deposition of the 39‐ to 43‐amino acid β‐amyloid peptide (Aβ) in the brain. C‐terminal fragments (CTFs) of amyloid precursor protein (APP) can accumulate in endosomally derived multivesicular bodies (MVBs). These intracellular structures contain intraluminal vesicles that are released from the cell as exosomes when the MVB fuses with the plasma membrane. Here we have investigated the role of exosomes in the processing of APP and show that these vesicles contain APP‐ CTFs, as well as Aβ. In addition, inhibition of γ‐secre‐ tase results in a significant increase in the amount of α‐ and β‐secretase cleavage, further increasing the amount of APP‐CTFs contained within these exosomes. We identify several key members of the secretase family of proteases (BACE, PS1, PS2, and ADAM10) to be localized in exosomes, suggesting they may be a previously unidentified site of APP cleavage. These results provide further evidence for a novel pathway in which APP fragments are released from cells and have implications for the analysis of APP processing and diagnostics for Alzheimer's disease.—Sharples, R. A., Vella, L. J., Nisbet, R. M., Naylor, R., Perez, K., Barnham, K. J., Masters, C. L., Hill, A. F. Inhibition of γ‐secretase causes increased secretion of amyloid precursor protein C‐terminal fragments in association with exosomes. FASEB J . 22, 1469–1478 (2008)
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Cites
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Cited by
Saman, S., Kim, W., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A. C., Alvarez, V. E., Lee, N. C. Y., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277061 · Cited by 985
Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy
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Extracellular vesicles round off communication in the nervous system
Budnik, V., Ruiz-Cañada, C., & Wendler, F. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.29 · Cited by 712
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625
Dinkins, M. B., Dasgupta, S., Wang, G., Zhu, G., & Bieberich, E. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.012 · Cited by 494
Metadata
- Authors
- Sharples, R. A., Vella, L. J., Nisbet, R. M., Naylor, R., Perez, K., Barnham, K. J., Masters, C. L., & Hill, A. F.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2008-01-02
- Volume
- 22
- Issue
- 5
- Pages
- 1469-1478
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1993103003
- Cited by
- 254
- References
- 80
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- closed
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