Evidence map›Paper›PMID 39629589›Full record

ArticleDisease models & mechanisms2024

Loss of function of VCP/TER94 causes neurodegeneration.

Kohei Tsumaki, Christian J F Bertens, Minoru Nakayama, Saya Kato, Yuki Jonao, Ayu Kuribayashi, Konosuke Sato, Shota Ishiyama, Momoko Asakawa, Riko Aihara and 6 more

Abstract read
In one paragraph

Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

16 authors.

Kohei TsumakiDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Christian J F BertensDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Minoru NakayamaDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Saya KatoDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Yuki JonaoDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Ayu KuribayashiDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Konosuke SatoDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Shota IshiyamaDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Momoko AsakawaDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Riko AiharaDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.
Yuki YoshiokaDepartment of Neuropathology, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Hidenori HommaDepartment of Neuropathology, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Hikari TanakaDepartment of Neuropathology, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Kyota FujitaDepartment of Neuropathology, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Hitoshi OkazawaDepartment of Neuropathology, Institute of Science Tokyo, Tokyo 113-8510, Japan.
Masaki SoneDepartment of Biomolecular Science, Faculty of Science, Toho University, Chiba 274-8510, Japan.ORCID 0000-0003-4563-9759

Funding

Japan Society for the Promotion of Science 26350982Toho UniversityTokyo Medical and Dental University
6 · The paper itself

Abstract

Variants in several genes are linked to human frontotemporal lobar degeneration (FTLD) associated with TDP43- and/or ubiquitin-positive inclusions. However, it is not yet clear whether the underlying mechanism is a gain-of-function or a loss-of-function one. To answer this question, we used Drosophila expressing double-stranded RNA against the FTLD-associated gene TER94 (an ortholog of VCP/p97) and found that the knockdown (KD) of this gene caused premature lethality, reduction in brain volume and alterations in the morphology of mushroom bodies. The changes caused by TER94 KD were rescued by wild-type TER94 but not by the human disease-linked A229E mutant, indicating that this mutant causes loss of function. Alterations were also observed in pupal brains and were partially rescued by co-expression of Mcm2, which is involved in control of the cell cycle, suggesting that dysregulation of neuronal proliferation caused the phenotypes. TER94 KD also caused the disappearance of TBPH (an ortholog of TDP43/TARDBP) from nuclei. These data from Drosophila genetics suggest that VCP-linked FTLD is caused by loss-of-function of VCP.

Indexed as

BrainDrosophila melanogasterDrosophila ProteinsValosin Containing ProteinAnimalsCell NucleusDNA-Binding ProteinsFrontotemporal Lobar DegenerationGene Knockdown TechniquesHumansLoss of Function MutationMushroom BodiesNerve DegenerationNeuronsOrgan SizePhenotypeDNA-Binding ProteinsDrosophila ProteinsTBPH protein, Drosophilater94 protein, DrosophilaValosin Containing ProteinDrosophilaFrontotemporal dementiaNeurodegenerationTDP43TER94VCP

Identifiers

PMID39629589
PMCPMC11698056

What Socratic holds

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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 Socratic graph.