Evidence map›Paper›PMID 25698727›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015

Stabilization of nontoxic Aβ-oligomers: insights into the mechanism of action of hydroxyquinolines in Alzheimer's disease.

Timothy M Ryan, Blaine R Roberts, Gawain McColl, Dominic J Hare, Philip A Doble, Qiao-Xin Li, Monica Lind, Anne M Roberts, Haydyn D T Mertens, Nigel Kirby and 6 more

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

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 72 citations in OpenAlex.

  1. The interactions of copper, glutamate, and cuproptosis: insights into brain health and Alzheimer's disease pathology.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
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  14. Acetylation of AβACS chemical neuroscience · 2020
    Article
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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

16 authors at 4 institutions in 1 country.

Timothy M RyanFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia, tmryan@unimelb.edu.au.
Blaine R RobertsFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Gawain McCollFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Dominic J HareFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia, Elemental Bio-imaging Facility, University of Technology Sydney, Broadway 2007, New South Wales, Australia.ORCID http://orcid.org/0000-0002-5922-7643
Philip A DobleElemental Bio-imaging Facility, University of Technology Sydney, Broadway 2007, New South Wales, Australia.
Qiao-Xin LiFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Monica LindFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Anne M RobertsFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Haydyn D T MertensAustralian Synchrotron, Clayton 3168, Victoria, Australia.ORCID http://orcid.org/0000-0002-5664-744X
Nigel KirbyAustralian Synchrotron, Clayton 3168, Victoria, Australia.
Chi L L PhamDepartment of Pharmacology, University of Melbourne, Parkville 3052, Victoria, Australia.
Mark G HindsBio21 Molecular Science and Technology Institute, University of Melbourne, Parkville 3052, Victoria, Australia, and School of Chemistry, University of Melbourne, Parkville 3052, Victoria, Australia.
Paul A AdlardFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Kevin J BarnhamFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia, Department of Pharmacology, University of Melbourne, Parkville 3052, Victoria, Australia, Bio21 Molecular Science and Technology Institute, University of Melbourne, Parkville 3052, Victoria, Australia, and.
Cyril C CurtainFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
Colin L MastersFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Victoria, Australia.
The University of Melbourne · AUAustralian Synchrotron · AUUniversity of Technology Sydney · AUMental Health Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The extracellular accumulation of amyloid β (Aβ) peptides is characteristic of Alzheimer's disease (AD). However, formation of diffusible, oligomeric forms of Aβ, both on and off pathways to amyloid fibrils, is thought to include neurotoxic species responsible for synaptic loss and neurodegeneration, rather than polymeric amyloid aggregates. The 8-hydroxyquinolines (8-HQ) clioquinol (CQ) and PBT2 were developed for their ability to inhibit metal-mediated generation of reactive oxygen species from Aβ:Cu complexes and have both undergone preclinical and Phase II clinical development for the treatment of AD. Their respective modes of action are not fully understood and may include both inhibition of Aβ fibrillar polymerization and direct depolymerization of existing Aβ fibrils. In the present study, we find that CQ and PBT2 can interact directly with Aβ and affect its propensity to aggregate. Using a combination of biophysical techniques, we demonstrate that, in the presence of these 8-HQs and in the absence of metal ions, Aβ associates with two 8-HQ molecules and forms a dimer. Furthermore, 8-HQ bind Aβ with an affinity of 1-10 μm and suppress the formation of large (>30 kDa) oligomers. The stabilized low molecular weight species are nontoxic. Treatment with 8-HQs also reduces the levels of in vivo soluble oligomers in a Caenorhabditis elegans model of Aβ toxicity. We propose that 8-HQs possess an additional mechanism of action that neutralizes neurotoxic Aβ oligomer formation through stabilization of small (dimeric) nontoxic Aβ conformers.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBenzothiazolesBiophysicsCaenorhabditis elegansCells, CulturedCerebral CortexChromatography, GelClioquinolEnzyme-Linked Immunosorbent AssayHumansHydroxyquinolinesMiceMicroscopy, ElectronNeuronsAmyloid beta-Peptidesamyloid beta-protein (1-42)BenzothiazolesClioquinolHydroxyquinolinesPBT2 compoundPeptide FragmentsThiazolesthioflavin TAlzheimer's diseaseamyloid beta peptidehydroxyquinolineoligomerPBT2toxicity

Identifiers

PMID25698727
PMCPMC6605585
OpenAlexW2053361295

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.