Evidence map›Paper›PMID 34234268›Full record

ArticleCommunications biology2021

Two human metabolites rescue a C. elegans model of Alzheimer's disease via a cytosolic unfolded protein response.

Priyanka Joshi, Michele Perni, Ryan Limbocker, Benedetta Mannini, Sam Casford, Sean Chia, Johnny Habchi, Johnathan Labbadia, Christopher M Dobson, Michele Vendruscolo

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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  3. Studying the mechanisms of neurodegeneration:Frontiers in cellular neuroscience · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Priyanka JoshiYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK. prijoshi@berkeley.edu.ORCID http://orcid.org/0000-0003-3419-2875
Michele PerniYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-7593-8376
Ryan LimbockerYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.
Benedetta ManniniYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-6812-7348
Sam CasfordYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.
Sean ChiaYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.
Johnny HabchiYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.
Johnathan LabbadiaDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, UK.
Christopher M DobsonYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-5445-680X
Michele VendruscoloYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, UK. mv245@cam.ac.uk.ORCID http://orcid.org/0000-0002-3616-1610
University of Cambridge · GBQB3 · USUnited States Military Academy · USUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Age-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer's disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

Indexed as

Disease Models, AnimalAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsCarnosineCytosolHSP40 Heat-Shock ProteinsHumansKynurenic AcidProtein AggregatesProtein Aggregation, PathologicalTranscription FactorsUnfolded Protein ResponseAmyloid beta-PeptidesCaenorhabditis elegans ProteinsCarnosineheat shock factor-1, C elegansHSP40 Heat-Shock ProteinsKynurenic AcidProtein AggregatesTranscription Factors

Identifiers

PMID34234268
PMCPMC8263720
OpenAlexW3182544940

What OpenQuestion holds

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LicenceCC BY
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.