Evidence map›Paper›PMID 24434516›Full record

ArticleCell death & disease2014

Inhibition of the AIF/CypA complex protects against intrinsic death pathways induced by oxidative stress.

N Doti, C Reuther, P L Scognamiglio, A M Dolga, N Plesnila, M Ruvo, C Culmsee

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 66 citations in OpenAlex.

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  19. Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy.Frontiers in molecular neuroscience · 2021
    Review
  20. Pyrrolo [3,4-Aging · 2020
    Article
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

7 authors at 3 institutions in 3 countries.

N Doti1] Institute of Biostructures and Bioimaging (IBB)-CNR, CIRPEB, Via Mezzocannone, 16, Naples 80134, Italy [2] Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, Marburg 35032, Germany [3] Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
C ReutherInstitute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, Marburg 35032, Germany.
P L ScognamiglioInstitute of Biostructures and Bioimaging (IBB)-CNR, CIRPEB, Via Mezzocannone, 16, Naples 80134, Italy.
A M DolgaInstitute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, Marburg 35032, Germany.
N Plesnila1] Department of Neurodegeneration, Royal College of Surgeons in Ireland, Dublin 2, Ireland [2] Institute for Stroke and Dementia Research (ISD), University of Munich Medical School-Campus Großhadern, Max-Lebsche Platz 30, Munich D-81377, Germany.
M RuvoInstitute of Biostructures and Bioimaging (IBB)-CNR, CIRPEB, Via Mezzocannone, 16, Naples 80134, Italy.
C CulmseeInstitute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, Marburg 35032, Germany.
Institute of Biostructure and Bioimaging · ITPhilipps University of Marburg · DERoyal College of Surgeons in Ireland · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Delayed neuronal cell death largely contributes to the progressive infarct development and associated functional impairments after cerebral ischemia or brain trauma. Previous studies exposed a key role for the interaction of the mitochondrial protein apoptosis-inducing factor (AIF) and cytosolic cyclophilin A (CypA) in pathways of programmed cell death in neurons in vitro and in vivo. These studies suggested that pro-apoptotic activities of AIF, such as its translocation to the nucleus and subsequent DNA degradation, depend on the physical interaction of AIF with CypA. Hence, this protein complex may represent a new pharmacological target for inhibiting the lethal action of AIF on the brain tissue. In this study, we show that the AIF amino-acid residues 370-394 mediate the protein complex formation of AIF with CypA. The synthetic AIF(370-394) peptide inhibited AIF/CypA complex formation in vitro by binding CypA with a K(D) of 12 μM. Further, the peptide exerted pronounced neuroprotective effects in a model of glutamate-induced oxidative stress in cultured HT-22 cells. In this model system of AIF-dependent cell death, the AIF(370-394) peptide preserved mitochondrial integrity, as detected by measurements of the mitochondrial membrane potential and quantification of mitochondrial fragmentation. Further, the AIF(370-394) peptide inhibited perinuclear accumulation of fragmented mitochondria, mitochondrial release of AIF to the nucleus and glutamate-induced cell death to a similar extent as CypA-siRNA. These data indicate that the targeting of the AIF-CypA axis is an effective strategy of neuroprotection.

Indexed as

ApoptosisOxidative StressAmino Acid MotifsApoptosis Inducing FactorCyclophilin ADown-RegulationHumansMitochondriaNeuronsProtein BindingApoptosis Inducing FactorCyclophilin A

Identifiers

PMID24434516
PMCPMC4040673
OpenAlexW2014202579

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.