Evidence map›Paper›PMID 26884339›Full record

ArticleThe Journal of biological chemistry2016

Clusterin Binds to Aβ1-42 Oligomers with High Affinity and Interferes with Peptide Aggregation by Inhibiting Primary and Secondary Nucleation.

Marten Beeg, Matteo Stravalaci, Margherita Romeo, Arianna Dorotea Carrá, Alfredo Cagnotto, Alessandro Rossi, Luisa Diomede, Mario Salmona, Marco Gobbi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
5.2field-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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Clusterin is enriched in plaque-associated astrocytes and localizes to synapses in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  10. Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
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8 more citing papers are in PubMed but not listed here.

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

9 authors at 1 institution in 1 country.

Marten BeegFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Matteo StravalaciFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Margherita RomeoFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Arianna Dorotea CarráFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Alfredo CagnottoFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Alessandro RossiFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Luisa DiomedeFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Mario SalmonaFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy.
Marco GobbiFrom the Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy marco.gobbi@marionegri.it.ORCID http://orcid.org/0000-0003-1014-6225
Mario Negri Institute for Pharmacological Research · IT

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
NIH HHS P40 OD010440
6 · The paper itself

Abstract

The aggregation of amyloid β protein (Aβ) is a fundamental pathogenic mechanism leading to the neuronal damage present in Alzheimer disease, and soluble Aβ oligomers are thought to be a major toxic culprit. Thus, better knowledge and specific targeting of the pathways that lead to these noxious species may result in valuable therapeutic strategies. We characterized some effects of the molecular chaperone clusterin, providing new and more detailed evidence of its potential neuroprotective effects. Using a classical thioflavin T assay, we observed a dose-dependent inhibition of the aggregation process. The global analysis of time courses under different conditions demonstrated that clusterin has no effect on the elongation rate but mainly interferes with the nucleation processes (both primary and secondary), reducing the number of nuclei available for further fibril growth. Then, using a recently developed immunoassay based on surface plasmon resonance, we obtained direct evidence of a high-affinity (KD= 1 nm) interaction of clusterin with biologically relevant Aβ1-42oligomers, selectively captured on the sensor chip. Moreover, with the same technology, we observed that substoichiometric concentrations of clusterin prevent oligomer interaction with the antibody 4G8, suggesting that the chaperone shields hydrophobic residues exposed on the oligomeric assemblies. Finally, we found that preincubation with clusterin antagonizes the toxic effects of Aβ1-42oligomers, as evaluated in a recently developedin vivomodel inCaenorhabditis elegans.These data substantiate the interaction of clusterin with biologically active regions exposed on nuclei/oligomers of Aβ1-42, providing a molecular basis for the neuroprotective effects of the chaperone.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBiological AssayCaenorhabditis elegansClusterinHumansKineticsLarvaNeuroprotective AgentsPeptide FragmentsPharynxProtein AggregatesProtein Aggregation, PathologicalProtein BindingAmyloid beta-Peptidesamyloid beta-protein (1-42)CLU protein, humanClusterinNeuroprotective AgentsPeptide FragmentsProtein AggregatesAlzheimer diseaseamyloid β (Aβ)Caenorhabditis eleganschaperoneclusterinkineticskinetics of fibril formationsurface plasmon resonance (SPR)

Identifiers

PMID26884339
PMCPMC4807280
OpenAlexW2277380679

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.