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Cited by 875

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain

Open access
Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., De Saint Andrieu, P., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E., Holsztynska, E. J., Hu, K. L., Johnson‐Wood, K. L., Kennedy, S. L., Kholodenko, D., Knops, J. E., Latimer, L. H., Lee, M., Liao, Z., Lieberburg, I. M., Motter, R. N., Mutter, L. C., Nietz, J., Quinn, K. P., Sacchi, K. L., Seubert, P. A., Shopp, G. M., Thorsett, E. D., Tung, J. S., Wu, J., Yang, S., Yin, C. T., Schenk, D. B., May, P. C., Altstiel, L. D., Bender, M. H., Boggs, L. N., Britton, T. C., Clemens, J. C., Czilli, D. L., Dieckman‐McGinty, D. K., Droste, J. J., Fuson, K. S., Gitter, B. D., Hyslop, P. A., Johnstone, E. M., Li, W‐Y., Little, S. P., Mabry, T. E., Miller, F. D., Ni, B., Nissen, J. S., Porter, W. J., Potts, B. D., Reel, J. K., Stephenson, D., Su, Y., Shipley, L. A., Whitesitt, C. A., Yin, T., Audia, J. E.·2001·Journal of Neurochemistry
DOI 10.1046/j.1471-4159.2001.00012.x
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Abstract

Converging lines of evidence implicate the beta‐amyloid peptide (Aβ) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce Aβ production by functionally inhibiting γ‐secretase, the activity responsible for the carboxy‐terminal cleavage required for Aβ production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon Aβ production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N‐[N‐(3,5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester, to mice transgenic for human APP V717F reduces brain levels of Aβ in a dose‐dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain Aβ in vivo. Development of such novel functional γ‐secretase inhibitors will enable a clinical examination of the Aβ hypothesis that Aβ peptide drives the neuropathology observed in Alzheimer's disease.

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Authors
Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., De Saint Andrieu, P., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E., Holsztynska, E. J., Hu, K. L., Johnson‐Wood, K. L., Kennedy, S. L., Kholodenko, D., Knops, J. E., Latimer, L. H., Lee, M., Liao, Z., Lieberburg, I. M., Motter, R. N., Mutter, L. C., Nietz, J., Quinn, K. P., Sacchi, K. L., Seubert, P. A., Shopp, G. M., Thorsett, E. D., Tung, J. S., Wu, J., Yang, S., Yin, C. T., Schenk, D. B., May, P. C., Altstiel, L. D., Bender, M. H., Boggs, L. N., Britton, T. C., Clemens, J. C., Czilli, D. L., Dieckman‐McGinty, D. K., Droste, J. J., Fuson, K. S., Gitter, B. D., Hyslop, P. A., Johnstone, E. M., Li, W., Little, S. P., Mabry, T. E., Miller, F. D., Ni, B., Nissen, J. S., Porter, W. J., Potts, B. D., Reel, J. K., Stephenson, D., Su, Y., Shipley, L. A., Whitesitt, C. A., Yin, T., & Audia, J. E.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2001-01
Volume
76
Issue
1
Pages
173-181
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1046/j.1471-4159.2001.00012.x
OpenAlex
W1754645121
Cited by
875
References
7
FWCI
30.58
Type
journal article
Language
en
Open access
bronze

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.