Evidence map›Paper›PMID 27221467›Full record

ArticleScientific reports2016

MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer's disease.

Gang Wang, Yue Huang, Li-Ling Wang, Yong-Fang Zhang, Jing Xu, Yi Zhou, Guinevere F Lourenco, Bei Zhang, Ying Wang, Ru-Jing Ren and 2 more

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 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

78 citing papers in PubMed, 118 citations in OpenAlex.

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18 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

12 authors at 4 institutions in 2 countries.

Gang WangDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Yue HuangNeuroscience Research Australia &University of New South Wales, Randwick, 2031, New South Wales, Australia.
Li-Ling WangDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Yong-Fang ZhangResearch Laboratory of Cell Regulation, School of Medicine, Shanghai Jiaotong University, 280 South Chongqing Road, Shanghai 200025, China.
Jing XuDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Yi ZhouDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Guinevere F LourencoNeuroscience Research Australia &University of New South Wales, Randwick, 2031, New South Wales, Australia.
Bei ZhangDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Ying WangDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Ru-Jing RenDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Glenda M HallidayNeuroscience Research Australia &University of New South Wales, Randwick, 2031, New South Wales, Australia.
Sheng-Di ChenDepartment of Neurology &Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Shanghai Jiao Tong University · CNRuijin Hospital · CNUNSW Sydney · AUChinese Academy of Sciences · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MicroRNA-146a is upregulated in the brains of patients with Alzheimer's disease (AD). Here, we show that the rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is a target of microRNA-146a in neural cells. Knockdown of ROCK1 mimicked the effects of microRNA-146a overexpression and induced abnormal tau phosphorylation, which was associated with inhibition of phosphorylation of the phosphatase and tensin homolog (PTEN). The ROCK1/PTEN pathway has been implicated in the neuronal hyperphosphorylation of tau that occurs in AD. To determine the function of ROCK1 in AD, brain tissue from 17 donors with low, intermediate or high probability of AD pathology were obtained and analyzed. Data showed that ROCK1 protein levels were reduced and ROCK1 colocalised with hyperphosphorylated tau in early neurofibrillary tangles. Intra-hippocampal delivery of a microRNA-146a specific inhibitor (antagomir) into 5xFAD mice showed enhanced hippocampal levels of ROCK1 protein and repressed tau hyperphosphorylation, partly restoring memory function in the 5xFAD mice. Our in vitro and in vivo results confirm that dysregulation of microRNA-146a biogenesis contributes to tau hyperphosphorylation and AD pathogenesis, and inhibition of this microRNA could be a viable novel in vivo therapy for AD.

Indexed as

Alzheimer DiseaseAnimalsCell LineDisease Models, AnimalHumansMiceMicroRNAsPhosphorylationrho-Associated Kinasestau ProteinsMAPT protein, humanMapt protein, mouseMicroRNAsMIRN146 microRNA, humanMirn146 microRNA, mouserho-Associated KinasesROCK1 protein, humanRock1 protein, mousetau Proteins

Identifiers

PMID27221467
PMCPMC4879631
OpenAlexW2402354931

What OpenQuestion holds

Textmetadata
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.