Evidence map›Paper›PMID 37837732›Full record

ArticleNeurobiology of aging2023

Protein retention in the endoplasmic reticulum rescues Aβ toxicity in Drosophila.

James H Catterson, Lucy Minkley, Salomé Aspe, Sebastian Judd-Mole, Sofia Moura, Miranda C Dyson, Arjunan Rajasingam, Nathaniel S Woodling, Magda L Atilano, Mumtaz Ahmad and 3 more

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

Article in Neurobiology of aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 7 citations in OpenAlex.

  1. eLife · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Brain communications · 2024
    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

13 authors at 2 institutions in 2 countries.

James H CattersonInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK; Centre for Discovery Brain Sciences, UK Dementia Research Institute, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, Scotland, UK.
Lucy MinkleyInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Salomé AspeInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Sebastian Judd-MoleInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Sofia MouraInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Miranda C DysonInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Arjunan RajasingamInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Nathaniel S WoodlingInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Magda L AtilanoInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Mumtaz AhmadInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Claire S DurrantCentre for Discovery Brain Sciences, UK Dementia Research Institute, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, Scotland, UK.
Tara L Spires-JonesCentre for Discovery Brain Sciences, UK Dementia Research Institute, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, Scotland, UK.
Linda PartridgeInstitute of Healthy Ageing, Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany. Electronic address: l.partridge@ucl.ac.uk.
University College London · GBUK Dementia Research Institute · GB

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5M
NIH HHS P40 OD018537Wellcome Trust
6 · The paper itself

Abstract

Amyloid β (Aβ) accumulation is a hallmark of Alzheimer's disease. In adult Drosophila brains, human Aβ overexpression harms climbing and lifespan. It's uncertain whether Aβ is intrinsically toxic or activates downstream neurodegeneration pathways. Our study uncovers a novel protective role against Aβ toxicity: intra-endoplasmic reticulum (ER) protein accumulation with a focus on laminin and collagen subunits. Despite high Aβ, laminin B1 (LanB1) overexpression robustly counters toxicity, suggesting a potential Aβ resistance mechanism. Other laminin subunits and collagen IV also alleviate Aβ toxicity; combining them with LanB1 augments the effect. Imaging reveals ER retention of LanB1 without altering Aβ secretion. LanB1's rescue function operates independently of the IRE1α/XBP1 ER stress response. ER-targeted GFP overexpression also mitigates Aβ toxicity, highlighting broader ER protein retention advantages. Proof-of-principle tests in murine hippocampal slices using mouse Lamb1 demonstrate ER retention in transduced cells, indicating a conserved mechanism. Though ER protein retention generally harms, it could paradoxically counter neuronal Aβ toxicity, offering a new therapeutic avenue for Alzheimer's disease.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCollagenDrosophilaEndoplasmic ReticulumEndoplasmic Reticulum StressEndoribonucleasesHumansLamininMiceProtein Serine-Threonine KinasesAmyloid beta-PeptidesCollagenEndoribonucleasesLamininProtein Serine-Threonine KinasesAlzheimer’s diseaseAβ toxicityDrosophila melanogasterEndoplasmic reticulumER retentionLaminin

Identifiers

PMID37837732
PMCPMC10940166
OpenAlexW4386914382

What Socratic holds

Textmetadata
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 Socratic graph.