High throughput screens for the identification of compounds that alter the accumulation of the Alzheimer's amyloid β peptide (Aβ)
Abstract
Evidence gathered over the last two decades suggests that beta amyloid (Abeta), the predominant proteinaceous component of senile plaques, plays an early and critical role in the etiology and pathogenesis of Alzheimer's disease (AD). Thus, it is reasonable to hypothesize that compounds capable of reducing the accumulation of Abeta may be of value therapeutically. Additionally, compounds that influence Abeta accumulation may be useful as tools to further dissect the cellular pathways that regulate Abeta production and accumulation. To screen for compounds that affect Abeta levels, we have established high throughput, cell-based assays capable of the sensitive and selective detection of Abeta40 in parallel with the more amyloidogenic form of the peptide, Abeta42. To validate the approach, we examined the effects of several compounds previously identified to influence Abeta accumulation. Analysis of peptide accumulation following treatment with these compounds showed results similar to those previously published. Currently, we are using this assay to screen drugs that have already received FDA approval for the treatment of other diseases and over-the-counter natural product extracts. If compounds such as these can be identified that lower Abeta in the brain, they may represent one of the fastest and most cost effective methods to therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · see citing works
Jarrett, J. T., & Lansbury, P. T. (1993) · Cell · doi:10.1016/0092-8674(93)90635-4 · Cited by 2,178 · see citing works
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · see citing works
Suzuki, N., Cheung, T. T., Cai, X.-D., Odaka, A., Otvos, L., Eckman, C., Golde, T. E., & Younkin, S. G. (1994) · Science · doi:10.1126/science.8191290 · Cited by 1,471 · see citing works
Self-citationProduction of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447 · see citing works
Self-citationMechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 947 · see citing works
Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain
Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., Andrieu, P. D. S. I., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E. G., Holsztynska, E. J., et al. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00012.x · Cited by 870 · see citing works
Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide
Haass, C., & Selkoe, D. J. (1993) · Cell · doi:10.1016/0092-8674(93)90312-e · Cited by 833 · see citing works
The toxicity in vitro of β-amyloid protein
Iversen, L. L., Mortishire‐Smith, R. J., Pollack, S. J., & Shearman, M. S. (1995) · Biochemical Journal · doi:10.1042/bj3110001 · Cited by 425 · see citing works
Activation of protein kinase C inhibits cellular production of the amyloid beta-protein.
Hung, A. Y., Haass, C., Nitsch, R. M., Qiu, W. Q., Citron, M., Wurtman, R. J., Growdon, J. H., & Selkoe, D. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49409-x · Cited by 399 · see citing works
Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme*
Eckman, E., Reed, D. K., & Eckman, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007579200 · Cited by 345 · see citing works
Self-citationThe role of cholesterol in the biosynthesis of β-amyloid.
Frears, E. R., Stephens, D. J., Walters, C. E., Davies, H., & Austen, B. (1999) · Neuroreport · doi:10.1097/00001756-199906030-00014 · Cited by 323 · see citing works
Golde, T. E., Eckman, C. B., & Younkin, S. G. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00043-0 · Cited by 300 · see citing works
Self-citationProtein phosphorylation inhibits production of Alzheimer amyloid beta/A4 peptide.
Buxbaum, J. D., Koo, E. H., & Greengard, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.9195 · Cited by 272 · see citing works
The C‐Terminus of the β Protein is Critical in Amyloidogenesis a
Jarrett, J., Berger, E. P., & Lansbury, P. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb23043.x · Cited by 257 · see citing works
Calcium Ionophore Increases Amyloid .beta. Peptide Production by Cultured Cells
Querfurth, H. W., & Selkoe, D. J. (1994) · Biochemistry · doi:10.1021/bi00181a016 · Cited by 243 · see citing works
Haass, C., Hung, A. Y., Schlossmacher, M. G., Oltersdorf, T., Teplow, D. B., & Selkoe, D. J. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb23037.x · Cited by 123 · see citing works
Presenilin 1 Regulates Pharmacologically Distinct γ-Secretase Activities
Murphy, M. P., Uljon, S., Fraser, P. E., Fauq, A. H., Lookingbill, H. A., Findlay, K. A., Smith, T. E., Lewis, P. A., McLendon, D. C., Wang, R., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002812200 · Cited by 96 · see citing works
Self-citationThe release of Alzheimer's disease beta amyloid peptide is reduced by phorbol treatment.
Jacobsen, J. S., Spruyt, M. A., Brown, A. M., Sahasrabudhe, S. R., Blume, A. J., Vitek, M. P., Muenkel, H. A., & Sonnenberg‐Reines, J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37204-6 · Cited by 91 · see citing works
Querfurth, H. W., Jiang, J., Geiger, J. D., et al. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69041580.x · Cited by 80 · see citing works
The secretion of amyloid β-peptides is inhibited in the tacrine-treated human neuroblastoma cells
Lahiri, D. K., Farlow, M. R., & Sambamurti, K. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00236-8 · Cited by 76 · see citing works
Petanceska, S. S., & Gandy, S. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0732316.x · Cited by 57 · see citing works
Haugabook, S. J., Le, T. V., Yager, D., Zenk, B., Healy, B., Eckman, E. A., Prada, C.-M., Younkin, L. H., Murphy, P., Pinnix, I., et al. (2000) · The FASEB Journal · doi:10.1096/fj.00-0528fje · Cited by 57 · see citing works
Self-citationSambamurti, K., Sevlever, D., Koothan, T., Refolo, L. M., Pinnix, I., Gandhi, S., Onstead, L., Younkin, L. H., Prada, C.-M., Yager, D., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.38.26810 · Cited by 48 · see citing works
Self-citationNeurohormonal Signaling Pathways and the Regulation of Alzheimer β-Amyloid Precursor Metabolism
Gandy, S. (1999) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(99)00166-6 · Cited by 32 · see citing works
Koo, E. H. (1997) · PubMed · Cited by 19 · see citing works
Koo, E. H., & Greengard, P. (1997) · Molecular Medicine · doi:10.1007/bf03401673 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Still being checked.
- Authors
- Haugabook, S. J., Yager, D. M., Eckman, E. A., Golde, T. E., Younkin, S. G., & Eckman, C. B.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Eckman, C.B
- Venue
- Journal of Neuroscience Methods
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 108
- Issue
- 2
- Pages
- 171-179
- ISSN
- 0165-0270 (ISSN-L)
- OpenAlex
- W2068057673
- Semantic Scholar
- 5dd6ede2028feac6f1f4b25a8ac1fcff1b1eca36
- Cited by
- 39
- References
- 29
- Citations by year
- 2023: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Methods (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- amyloid-beta, Alzheimer's disease, high-throughput screening, cell-based assays, Aβ40, amyloid-beta 42, amyloid plaques, drug screening, natural extracts, FDA-approved drugs, amyloid accumulation
- MeSH terms
- Alzheimer Disease, Animals, Biological Assay, Cell Survival, Cells, Cultured, Drug Evaluation, Preclinical, Enzyme-Linked Immunosorbent Assay, Cricetinae, Humans, Peptide Fragments, Reproducibility of Results, Amyloid beta-Peptides, CHO Cells, Culture Media, Conditioned, Toxicity Tests, Neuroprotective Agents, Cell Culture Techniques, Drug-Related Side Effects and Adverse Reactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
