Evidence map›Paper›PMID 31144295›Full record

ArticleThe Journal of pathology2019

Loss of FBXO7 results in a Parkinson's-like dopaminergic degeneration via an RPL23-MDM2-TP53 pathway.

Simon Rw Stott, Suzanne J Randle, Sara Al Rawi, Paulina A Rowicka, Rebecca Harris, Bethany Mason, Jing Xia, Jeffrey W Dalley, Roger A Barker, Heike Laman

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

Article in The Journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. PI31 expression is neuroprotective in a mouse model of early-onset parkinsonism.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Review
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  9. Review
  10. The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance, and neuronal survival in mice.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  11. A Conserved Requirement forFrontiers in physiology · 2019
    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

10 authors at 2 institutions in 1 country.

Simon Rw StottJohn van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Suzanne J RandleDepartment of Pathology, University of Cambridge, Cambridge, UK.
Sara Al RawiDepartment of Pathology, University of Cambridge, Cambridge, UK.
Paulina A RowickaDepartment of Pathology, University of Cambridge, Cambridge, UK.
Rebecca HarrisDepartment of Pathology, University of Cambridge, Cambridge, UK.
Bethany MasonDepartment of Pathology, University of Cambridge, Cambridge, UK.
Jing XiaBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Jeffrey W DalleyBehavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
Roger A BarkerJohn van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Heike LamanDepartment of Pathology, University of Cambridge, Cambridge, UK.ORCID 0000-0002-6089-171X
University of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J007846/1Medical Research Council MC_PC_12009Parkinson's UK G-1701
6 · The paper itself

Abstract

The field of Parkinson's disease research has been impeded by the absence of animal models that clearly phenocopy the features of this neurodegenerative condition. Mutations in FBXO7/PARK15 are associated with both sporadic Parkinson's disease and a severe form of autosomal recessive early-onset Parkinsonism. Here we report that conditional deletion of Fbxo7 in the midbrain dopamine neurons results in an early reduction in striatal dopamine levels, together with a slow, progressive loss of midbrain dopamine neurons and onset of locomotor defects. Unexpectedly, a later compensatory response led to a near-full restoration of dopaminergic fibre innervation in the striatum, but nigral cell loss was irreversible. Mechanistically, there was increased expression in the dopamine neurons of FBXO7-interacting protein, RPL23, which is a sensor of ribosomal stress that inhibits MDM2, the negative regulator of p53. A corresponding activated p53 transcriptional signature biased towards pro-apoptotic genes was also observed. These data suggest that the neuroprotective role of FBXO7 involves its suppression of the RPL23-MDM2-p53 axis that promotes cell death in dopaminergic midbrain neurons. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Indexed as

Nerve DegenerationAnimalsBehavior, AnimalDisease Models, AnimalDopaminergic NeuronsF-Box ProteinsFemaleLocomotionMaleMesencephalonMice, Inbred C57BLMice, KnockoutMotor ActivityParkinson DiseaseProto-Oncogene Proteins c-mdm2Ribosomal ProteinsF-Box ProteinsFBXO7 protein, mouseMdm2 protein, mouseProto-Oncogene Proteins c-mdm2Ribosomal ProteinsRpl23 protein, mouseTrp53 protein, mouseTumor Suppressor Protein p53dopaminergic neuronsFBXO7/PARK15Parkinson's diseaseRpl23-Mdm2-p53 axis

Identifiers

PMID31144295
PMCPMC6790581
OpenAlexW2946952255

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.