Evidence map›Paper›PMID 25257175›Full record

ArticleCell death and differentiation2015

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

F M Menzies, M Garcia-Arencibia, S Imarisio, N C O'Sullivan, T Ricketts, B A Kent, M V Rao, W Lam, Z W Green-Thompson, R A Nixon and 4 more

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

Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
5.6field-weighted citation impact, top 4% 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

65 citing papers in PubMed, 121 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026
    Review
  5. Article
  6. Calcium Ions in the Physiology and Pathology of the Central Nervous System.International journal of molecular sciences · 2024
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Frontiers in neuroscience · 2023
    Review
  13. Article
  14. The group AInfectious microbes & diseases · 2022
    Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article

5 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

14 authors at 3 institutions in 2 countries.

F M MenziesDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
M Garcia-ArencibiaDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
S ImarisioDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
N C O'SullivanDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
T RickettsDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
B A Kent1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Translational and Cognitive Neuroscience Laboratory, MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
M V Rao1] Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA [3] Department of Cell Biology, New York University Langone Medical Center, New York, NY, USA.
W LamDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Z W Green-ThompsonDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
R A Nixon1] Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, USA [2] Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA [3] Department of Cell Biology, New York University Langone Medical Center, New York, NY, USA.
L M Saksida1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Translational and Cognitive Neuroscience Laboratory, MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
T J Bussey1] Department of Psychology, University of Cambridge, Cambridge, UK [2] Translational and Cognitive Neuroscience Laboratory, MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
C J O'KaneDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
D C RubinszteinDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
University of Cambridge · GBNathan Kline Institute for Psychiatric Research · USWellcome Trust · GB

Funding

Uncovering Alzheimer's disease risk mechanisms through neuron-specific analysis of autophagy and endosomal-lysosomal functionP01AG017617 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI NIXON, RALPH A. · 2000 to 2021
$40.0M
Medical Research Council MC_G1000734Medical Research Council MR/J006904/1NIA NIH HHS P01 AG017617Wellcome Trust 089703Wellcome Trust 095317Wellcome Trust 100140
6 · The paper itself

Abstract

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.

Indexed as

AnimalsAutophagyCalcium-Binding ProteinsCalpainDisease Models, AnimalDrosophilaDrosophila ProteinsFemaleGene Knockdown TechniquesHuntington DiseaseInbreedingMaleMiceMice, Inbred C57BLPeptidesSignal TransductionCalcium-Binding ProteinsCalpaincalpain A, DrosophilacalpastatinDrosophila ProteinsPeptidespolyglutamine

Identifiers

PMID25257175
PMCPMC4326573
OpenAlexW2000009880

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.