Cited by 657Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment Research

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NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo

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Eriksen, Jason L., Sagi, Sarah A., Smith, Tawnya E., Weggen, Sascha, Das, Pritam, McLendon, D.C., Ozols, Victor V., Jessing, Kevin W., Zavitz, Kenton H., Koo, Edward H., Golde, Todd E.·2003·Journal of Clinical Investigation

DOI 10.1172/jci18162PMC PMC166298

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Abstract

Epidemiologic studies demonstrate that long-term use of NSAIDs is associated with a reduced risk for the development of Alzheimer disease (AD). In this study, 20 commonly used NSAIDs, dapsone, and enantiomers of flurbiprofen were analyzed for their ability to lower the level of the 42-amino-acid form of amyloid beta protein (Abeta42) in a human H4 cell line. Thirteen of the NSAIDs and the enantiomers of flurbiprofen were then tested in acute dosing studies in amyloid beta protein precursor (APP) transgenic mice, and plasma and brain levels of Abeta and the drug were evaluated. These studies show that (a). eight FDA-approved NSAIDs lower Abeta42 in vivo, (b). the ability of an NSAID to lower Abeta42 levels in cell culture is highly predicative of its in vivo activity, (c). in vivo Abeta42 lowering in mice occurs at drug levels achievable in humans, and (d). there is a significant correlation between Abeta42 lowering and levels of ibuprofen. Importantly, flurbiprofen and its enantiomers selectively lower Abeta42 levels in broken cell gamma-secretase assays, indicating that these compounds directly target the gamma-secretase complex that generates Abeta from APP. Of the compounds tested, meclofenamic acid, racemic flurbiprofen, and the purified R and S enantiomers of flurbiprofen lowered Abeta42 levels to the greatest extent. Because R-flurbiprofen reduces Abeta42 levels by targeting gamma-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Abeta42 lowering agent.

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Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516
Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity
Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., & Selkoe, D. J. (1999) · Nature · doi:10.1038/19077 · Cited by 1,959
Statins and the risk of dementia
Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S. S., & Drachman, D. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03155-x · Cited by 1,764
Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,486

Show all 52 references

Research works printed but not linked: 3

Wechter, 2000, Cancer Res., 60, 2203
Edbauer, 2003, Nat. Cell Biol., 7, 7
Murray, 2000, Clin. Pharmacol. Ther., 67, 103

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Authors: Eriksen, J. L., Sagi, S. A., Smith, T. E., Weggen, S., Das, P., McLendon, D. C., Ozols, V. V., Jessing, K. W., Zavitz, K. H., Koo, E. H., & Golde, T. E.
Affiliations: Mayo Clinic (US)
University of California San Diego (US)
Corresponding author: Golde, Todd E.
ORCID: Eriksen, Jason L.
Weggen, Sascha
Das, Pritam
Koo, Edward H.
Golde, Todd E.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2003-08-01
Volume: 112
Issue: 3
Pages: 440-449
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci18162
PMC: PMC166298
OpenAlex: W2103071556
Cited by: 634
References: 52
Citations by year: 2026: 7 · 2025: 12 · 2024: 11 · 2023: 11 · 2022: 15 · 2021: 20 · 2020: 14 · 2019: 15 · 2018: 11 · 2017: 18 · 2016: 25 · 2015: 18 · 2014: 31 · 2013: 32 · 2012: 37
FWCI: 23.24
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Mayo Foundation for Medical Education and Research
National Institutes of Health
National Institute on Aging (P01AG020206, T32AG000216)
National Institute of Neurological Disorders and Stroke (R01NS039072)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: nonsteroidal anti-inflammatory drugs, gamma-secretase, amyloid-beta 42, Alzheimer's disease, APP transgenic mice, ibuprofen, meclofenamic acid, dapsone, cyclooxygenase inhibition, drug repurposing
MeSH terms: Alzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Brain, Cell Line, Female, Flurbiprofen, Humans, Meclofenamic Acid, Mice, Transgenic, Peptide Fragments, Endopeptidases, Protease Inhibitors, Stereoisomerism, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Mice, Amyloid Precursor Protein Secretases

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NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo

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