Evidence map›Paper›PMID 26790818›Full record

ArticleScientific reports2016

Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of α-tubulin acetylation and FGF-21 up-regulation.

Zhifei Wang, Yan Leng, Junyu Wang, Hsiao-Mei Liao, Joel Bergman, Peter Leeds, Alan Kozikowski, De-Maw Chuang

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

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% 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

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.

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14 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

8 authors at 4 institutions in 2 countries.

Zhifei WangSchool of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Yan LengMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA.
Junyu WangMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA.
Hsiao-Mei LiaoMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA.
Joel BergmanDrug Discovery Program, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Peter LeedsMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA.
Alan KozikowskiDrug Discovery Program, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
De-Maw ChuangMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA.
National Institutes of Health · USUniversity of Illinois Chicago · USNational Institute of Mental Health · USShanghai University of Traditional Chinese Medicine · CN

Funding

MECHANISMS OF ACTION OF PSYCHOACTIVE DRUGSZ01MH002468 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI CHUANG, DE-MAW · 1990 to 2008
$3.9M
Intramural NIH HHS Z01 MH002468
6 · The paper itself

Abstract

Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as α-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction, and ameliorated neuronal cell death in MCAO rats. These beneficial effects lasted at least three days after MCAO. Notably, when given at 24 hours after MCAO, TubA still exhibited significant protection. Levels of acetylated α-tubulin were decreased in the ischemic hemisphere on Days 1 and 3 after MCAO, and were significantly restored by TubA. MCAO markedly downregulated fibroblast growth factor-21 (FGF-21) and TubA significantly reversed this downregulation. TubA also mitigated impaired FGF-21 signaling in the ischemic hemisphere, including up-regulating β-Klotho, and activating ERK and Akt/GSK-3β signaling pathways. In addition, both TubA and exogenous FGF-21 conferred neuroprotection and restored mitochondrial trafficking in rat cortical neurons against glutamate-induced excitotoxicity. Our findings suggest that the neuroprotective effects of TubA likely involve HDAC6 inhibition and the subsequent up-regulation of acetylated α-tubulin and FGF-21.

Indexed as

AcetylationAnimalsBrain InfarctionCell DeathDisease Models, AnimalFibroblast Growth FactorsGene Expression RegulationGlutamic AcidHistone Deacetylase InhibitorsHydroxamic AcidsIndolesMitochondriaNeuritesNeuronsNeuroprotective AgentsRatsfibroblast growth factor 21Fibroblast Growth FactorsGlutamic AcidHistone Deacetylase InhibitorsHydroxamic AcidsIndolesNeuroprotective Agentstubastatin ATubulin

Identifiers

PMID26790818
PMCPMC4726180
OpenAlexW2396184091

What OpenQuestion holds

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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.