Evidence map›Paper›PMID 10567229›Full record

ArticleThe Biochemical journal1999

Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion.

T Borchardt, J Camakaris, R Cappai, C L Masters, K Beyreuther, G Multhaup

Open access · greenAbstract read
PubMed Full text at PMC
In one paragraph

Article in The Biochemical journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 171 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Review
  7. Review
  8. Copper homeostasis and the ubiquitin proteasome system.Metallomics : integrated biometal science · 2023
    Review
  9. Article
  10. Article
  11. Defining the Neuropathological Aggresome acrossThe journal of physical chemistry. B · 2021
    Review
  12. Article
  13. Review
  14. Review
  15. Metal Ion Effects on Aβ and Tau Aggregation.International journal of molecular sciences · 2018
    Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

T BorchardtZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
J Camakaris
R Cappai
C L Masters
K Beyreuther
G Multhaup
Heidelberg University · DEMental Health Research Institute · AUUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Previous studies have demonstrated that amyloid precursor protein (APP) can bind and reduce Cu(II) to Cu(I), leading to oxidative modification of APP. In the present study we show that adding copper to Chinese-hamster ovary (CHO) cells greatly reduced the levels of amyloid Abeta peptide (Abeta) both in parental CHO-K1 and in copper-resistant CHO-CUR3 cells, which have lower intracellular copper levels. Copper also caused an increase in the secretion of the APP ectodomain, indicating that the large decrease in Abeta release was not due to a general inhibition in protein secretion. There was an increase in intracellular full-length APP levels which paralleled the decrease in Abeta generation, suggesting the existence of two distinct regulating mechanisms, one acting on Abeta production and the other on APP synthesis. Maximal inhibition of Abeta production and stimulation of APP secretion was achieved in CHO-K1 cells at about 10 microM copper and in CHO-CUR3 cells at about 50 microM copper. This dose 'window of opportunity' at which copper promoted the non-amyloidogenic pathway of APP was confirmed by an increase in the non-amyloidogenic p3 fragment produced by alpha-secretase cleavage. Our findings suggest that copper or copper agonists might be useful tools to discover novel targets for anti-Alzheimer drugs and may prove beneficial for the prevention of Alzheimer's disease.

Indexed as

Amino Acid SequenceAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCopperDose-Response Relationship, DrugMolecular Sequence DataPeptide FragmentsPrecipitin TestsProtein Processing, Post-TranslationalRecombinant ProteinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCopperPeptide FragmentsRecombinant Proteins

Identifiers

PMID10567229
PMCPMC1220664
OpenAlexW1993231460

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.