Evidence map›Paper›PMID 34416891›Full record

ArticleMolecular brain2021

Sodium valproate increases activity of the sirtuin pathway resulting in beneficial effects for spinocerebellar ataxia-3 in vivo.

Maxinne Watchon, Luan Luu, Katherine J Robinson, Kristy C Yuan, Alana De Luca, Hannah J Suddull, Madelaine C Tym, Gilles J Guillemin, Nicholas J Cole, Garth A Nicholson and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular brain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
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  5. Review
  6. Review
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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.

Maxinne WatchonCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.ORCID 0000-0002-8400-4994
Luan LuuCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Katherine J RobinsonCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.ORCID 0000-0001-9603-2696
Kristy C YuanCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Alana De LucaCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Hannah J SuddullCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Madelaine C TymCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Gilles J GuilleminCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Nicholas J ColeCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Garth A NicholsonCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Roger S ChungCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Albert LeeCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia.
Angela S LairdCentre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Level 1, 2 Technology Place, Sydney, NSW 2109, Australia. angela.laird@mq.edu.au.ORCID 0000-0002-6860-9192

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3) is a fatal neurodegenerative disease that impairs control and coordination of movement. Here we tested whether treatment with the histone deacetylase inhibitor sodium valproate (valproate) prevented a movement phenotype that develops in larvae of a transgenic zebrafish model of the disease. We found that treatment with valproate improved the swimming of the MJD zebrafish, affected levels of acetylated histones 3 and 4, but also increased expression of polyglutamine expanded human ataxin-3. Proteomic analysis of protein lysates generated from the treated and untreated MJD zebrafish also predicted that valproate treatment had activated the sirtuin longevity signaling pathway and this was confirmed by findings of increased SIRT1 protein levels and sirtuin activity in valproate treated MJD zebrafish and HEK293 cells expressing ataxin-3 84Q, respectively. Treatment with resveratrol (another compound known to activate the sirtuin pathway), also improved swimming in the MJD zebrafish. Co-treatment with valproate alongside EX527, a SIRT1 activity inhibitor, prevented induction of autophagy by valproate and the beneficial effects of valproate on the movement in the MJD zebrafish, supporting that they were both dependent on sirtuin activity. These findings provide the first evidence of sodium valproate inducing activation of the sirtuin pathway. Further, they indicate that drugs that target the sirtuin pathway, including sodium valproate and resveratrol, warrant further investigation for the treatment of MJD and related neurodegenerative diseases.

Indexed as

AcetylationAnimalsAnimals, Genetically ModifiedAtaxin-3AutophagyCarbazolesDisease Models, AnimalDrug Evaluation, PreclinicalDrug SynergismGenes, ReporterHEK293 CellsHistone Deacetylase InhibitorsHistonesHumansMachado-Joseph DiseasePeptides6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamideAtaxin-3ATXN3 protein, humanCarbazolesHistone Deacetylase InhibitorsHistonesPeptidespolyglutamineRecombinant Fusion ProteinsRepressor ProteinsResveratrolSIRT1 protein, humanSirtuin 1SirtuinsValproic AcidZebrafish ProteinsMachado−Joseph diseaseNeurodegenerationPolyglutamineSodium valproateSpinocerebellar ataxia−3Valproic acidZebrafish

Identifiers

PMID34416891
PMCPMC8377983

What OpenQuestion 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 OpenQuestion graph.