Evidence map›Paper›PMID 25064321›Full record

ArticleFree radical biology & medicine2014

Oxidative stress-mediated activation of extracellular signal-regulated kinase contributes to mild cognitive impairment-related mitochondrial dysfunction.

Xueqi Gan, Long Wu, Shengbin Huang, Changjia Zhong, Honglian Shi, Guangyue Li, Haiyang Yu, Russell Howard Swerdlow, John Xi Chen, Shirley ShiDu Yan

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

Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
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  11. Mitochondria and Mitochondrial Cascades in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2018
    Review
  12. Article
  13. [Influences of vibration on rapid osteogenic response of osteoblasts].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2017
    Article
  14. Article
  15. Mitochondrial Perturbation in Alzheimer's Disease and Diabetes.Progress in molecular biology and translational science · 2017
    Review
  16. Mitochondria, Cybrids, Aging, and Alzheimer's Disease.Progress in molecular biology and translational science · 2017
    Review
  17. Article
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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

10 authors at 5 institutions in 2 countries.

Xueqi GanDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Cheng Du 610041, China.
Long WuDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA.
Shengbin HuangDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Cheng Du 610041, China.
Changjia ZhongDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA.
Honglian ShiDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA.
Guangyue LiDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Cheng Du 610041, China.
Haiyang YuState Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Cheng Du 610041, China.
Russell Howard SwerdlowDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
John Xi ChenDepartment of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Shirley ShiDu YanDepartment of Pharmacology and Toxicology and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA. Electronic address: shidu@ku.edu.
University of Kansas · USSichuan University · CNMemorial Sloan Kettering Cancer Center · USState Key Laboratory of Oral DiseasesUniversity of Kansas Medical Center · US

Funding

University of Kansas Alzheimer's Disease Core CentersP30AG035982 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SWERDLOW, RUSSELL H. · 2011 to 2020
$16.6M
Role of Cyclophilin D in Abeta-induced synaptic injuryR37AG037319 · NIA · UNIVERSITY OF KANSAS LAWRENCE · PI YAN, SHIRLEY SHIDU · 2010 to 2019
$3.1M
Role of LRG-47 (Irgm1) in EAER01NS065482 · NINDS · UNIVERSITY OF KANSAS LAWRENCE · PI YAN, SHIRLEY SHIDU · 2010 to 2014
$1.6M
NIA NIH HHS NIA P30AG035982NIA NIH HHS P30 AG035982NIA NIH HHS R37 AG037319NIA NIH HHS R37AG037319NINDS NIH HHS NS R01NS65482NINDS NIH HHS R01 NS065482
6 · The paper itself

Abstract

Mild cognitive impairment (MCI) occurs during the predementia stage of Alzheimer disease (AD) and is characterized by a decline in cognitive abilities that frequently represents a transition between normal cognition and AD dementia. Its pathogenesis is not well understood. Here, we demonstrate the direct consequences and potential mechanisms of oxidative stress and mitochondrial dynamic and functional defects in MCI-derived mitochondria. Using a cytoplasmic hybrid (cybrid) cell model in which mitochondria from MCI or age-matched non-MCI subjects were incorporated into a human neuronal cell line depleted of endogenous mitochondrial DNA, we evaluated the mitochondrial dynamics and functions, as well as the role of oxidative stress in the resultant cybrid lines. We demonstrated that increased expression levels of mitofusin 2 (Mfn2) are markedly induced by oxidative stress in MCI-derived mitochondria along with aberrant mitochondrial functions. Inhibition of oxidative stress rescues MCI-impaired mitochondrial fusion/fission balance as shown by the suppression of Mfn2 expression, attenuation of abnormal mitochondrial morphology and distribution, and improvement in mitochondrial function. Furthermore, blockade of MCI-related stress-mediated activation of extracellular signal-regulated kinase (ERK) signaling not only attenuates aberrant mitochondrial morphology and function but also restores mitochondrial fission and fusion balance, in particular inhibition of overexpressed Mfn2. Our results provide new insights into the role of the oxidative stress-ERK-Mfn2 signal axis in MCI-related mitochondrial abnormalities, indicating that the MCI phase may be targetable for the development of new therapeutic approaches that improve mitochondrial function in age-related neurodegeneration.

Indexed as

AgedAlzheimer DiseaseCells, CulturedCognitionCognitive DysfunctionEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleFlavonoidsGTP PhosphohydrolasesHumansMaleMembrane Potential, MitochondrialMiddle AgedMitochondriaMitochondrial Dynamics2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-oneExtracellular Signal-Regulated MAP KinasesFlavonoidsGTP PhosphohydrolasesMFN2 protein, humanMitochondrial ProteinsProtein Kinase InhibitorsRNA, Small InterferingCybrid cellsERKFree radicalsMfn2Mild cognitive impairmentMitochondrial fissionMitochondrial fusionOxidative stress

Identifiers

PMID25064321
PMCPMC4392773
OpenAlexW2046949855

What OpenQuestion holds

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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.