Evidence map›Paper›PMID 24252614›Full record

ArticleBiochimica et biophysica acta2014

Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer's disease cybrid cell.

Xueqi Gan, Shengbin Huang, Long Wu, Yongfu Wang, Gang Hu, Guangyue Li, Hongju Zhang, Haiyang Yu, Russell Howard Swerdlow, John Xi Chen and 1 more

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

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

105 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.

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45 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

11 authors at 4 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.
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.
Long WuDepartment of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA.
Yongfu WangDepartment of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA.
Gang HuDepartment 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.
Hongju ZhangDepartment of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS 66047, USA.
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 1003, 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 · USMemorial Sloan Kettering Cancer Center · USSichuan University · CNUniversity 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
Structural and Functional Properties of cyclophilin D and Abeta interaction.R01GM095355 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI YAN, SHIRLEY SHIDU · 2010 to 2013
$1.5M
NIA NIH HHS P30 AG035982NIA NIH HHS P30AG035982NIA NIH HHS R37 AG037319NIA NIH HHS R37AG037319NIGMS NIH HHS R01 GM095355NIGMS NIH HHS R01GM095355
6 · The paper itself

Abstract

Mitochondrial dysfunction is an early pathological feature of Alzheimer's disease (AD). The underlying mechanisms and strategies to repair it remain unclear. Here, we demonstrate for the first time the direct consequences and potential mechanisms of mitochondrial functional defects associated with abnormal mitochondrial dynamics in AD. Using cytoplasmic hybrid (cybrid) neurons with incorporated platelet mitochondria from AD and age-matched non-AD human subjects into mitochondrial DNA (mtDNA)-depleted neuronal cells, we observed that AD cybrid cells had significant changes in morphology and function; such changes associate with altered expression and distribution of dynamin-like protein (DLP1) and mitofusin 2 (Mfn2). Treatment with antioxidant protects against AD mitochondria-induced extracellular signal-regulated kinase (ERK) activation and mitochondrial fission-fusion imbalances. Notably, inhibition of ERK activation not only attenuates aberrant mitochondrial morphology and function but also restores the mitochondrial fission and fusion balance. These effects suggest a role of oxidative stress-mediated ERK signal transduction in modulation of mitochondrial fission and fusion events. Further, blockade of the mitochondrial fission protein DLP1 by a genetic manipulation with a dominant negative DLP1 (DLP1(K38A)), its expression with siRNA-DLP1, or inhibition of mitochondrial division with mdivi-1 attenuates mitochondrial functional defects observed in AD cybrid cells. Our results provide new insights into mitochondrial dysfunction resulting from changes in the ERK-fission/fusion (DLP1) machinery and signaling pathway. The protective effect of mdivi-1 and inhibition of ERK signaling on maintenance of normal mitochondrial structure and function holds promise as a potential novel therapeutic strategy for AD.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAntioxidantsDynaminsExtracellular Signal-Regulated MAP KinasesFemaleGTP PhosphohydrolasesHumansHybrid CellsImmunoblottingMaleMicrotubule-Associated ProteinsMiddle AgedMitochondriaMitochondrial Dynamics3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinoneAntioxidantsDNM1L protein, humanDynaminsExtracellular Signal-Regulated MAP KinasesGTP PhosphohydrolasesMAPK1 protein, humanMicrotubule-Associated ProteinsMitochondrial ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3ProbucolQuinazolinonesReactive Oxygen SpeciesADAlzheimer's diseaseAmyloid beta peptideAβCcOCybrid cellsCytochrome c oxidaseDLP1Dynamin-like proteinERKExtracellular signal-regulated kinaseHDHuntington diseaseMfn2Mitochondrial DNAMitochondrial fission and fusionMitofusin 2mtDNAParkinson diseasePDReactive oxygen speciesROSTetramethylrhodaminemethylesterTMRM

Identifiers

PMID24252614
PMCPMC3991235
OpenAlexW2032817697

What OpenQuestion holds

Textmetadata
LicenceTDM
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.