Evidence map›Paper›PMID 26928464›Full record

ArticleNature medicine2016

Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis.

SungWon Song, Carlos J Miranda, Lyndsey Braun, Kathrin Meyer, Ashley E Frakes, Laura Ferraiuolo, Shibi Likhite, Adam K Bevan, Kevin D Foust, Michael J McConnell and 2 more

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

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

82 citing papers in PubMed, 141 citations in OpenAlex.

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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

SungWon Song *Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Carlos J Miranda *Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Lyndsey BraunCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Kathrin MeyerCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Ashley E FrakesCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Laura FerraiuoloCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Shibi LikhiteCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Adam K BevanCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Kevin D FoustCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Michael J McConnellDept. of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
Christopher M WalkerCenter for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Brian K KasparCenter for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Nationwide Children's Hospital · USUniversity of Virginia · US

Funding

ENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2008 to 2018
$6.8M
Delivery of therapeutic genes in motor neuron diseaseRC2NS069476 · NINDS · OHIO STATE UNIVERSITY · PI BURGHES, ARTHUR H. M., CLEVELAND, DON W · 2009 to 2010
$3.4M
Role of Potent Trophic Factors on Glia and Motor Neurons in ALSR01NS064492 · NINDS · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI KASPAR, BRIAN K. · 2009 to 2013
$1.5M
Training in neuromuscular diseasesT32NS077984 · NINDS · OHIO STATE UNIVERSITY · PI GUTTRIDGE, DENIS C, MENDELL, JERRY ROY · 2012 to 2016
$946k
NINDS NIH HHS P30 NS055077NINDS NIH HHS P30NS055077NINDS NIH HHS R01 NS064492NINDS NIH HHS R01-NS644912NINDS NIH HHS RC2 NS069476NINDS NIH HHS RC2-NS69476NINDS NIH HHS T32 NS077984
6 · The paper itself

Abstract

Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non-cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte-mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity.

Indexed as

AgedAged, 80 and overAmyotrophic Lateral SclerosisAnimalsAstrocytesCadaverCell DeathDisease Models, AnimalFemaleGene Expression RegulationHistocompatibility Antigens Class IHumansMaleMiceMice, TransgenicMiddle AgedHistocompatibility Antigens Class IHLA-F antigensKIR3DL2 protein, humanReceptors, KIR3DL2Superoxide Dismutase

Identifiers

PMID26928464
PMCPMC4823173
OpenAlexW2290753804

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.