Evidence map›Paper›PMID 33374005›Full record

ArticleBrain : a journal of neurology2021

Cell type-specific transcriptomics identifies neddylation as a novel therapeutic target in multiple sclerosis.

Kicheol Kim, Anne-Katrin Pröbstel, Ryan Baumann, Julia Dyckow, James Landefeld, Elva Kogl, Lohith Madireddy, Rita Loudermilk, Erica L Eggers, Sneha Singh and 7 more

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

Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 16% 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

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  11. Discovering Root Causal Genes with High Throughput Perturbations.bioRxiv : the preprint server for biology · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Neddylation Regulation of Immune Responses.Research (Washington, D.C.) · 2023
    Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 3 countries.

Kicheol KimWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Anne-Katrin PröbstelWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Ryan BaumannWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Julia DyckowDepartment of Neurology and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Interdisciplinary Center for Neurosciences, University of Heidelberg, Mannheim, Germany.
James LandefeldWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Elva KoglWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Lohith MadireddyWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Rita LoudermilkWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Erica L EggersWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Sneha SinghWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Stacy J CaillierWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Stephen L HauserWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Bruce A C CreeWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
UCSF MS-EPIC Team
Lucas SchirmerDepartment of Neurology and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Interdisciplinary Center for Neurosciences, University of Heidelberg, Mannheim, Germany.
Michael R WilsonWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Sergio E BaranziniWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
University of California, San Francisco · USHeidelberg University · DE

Funding

The Role of B cells in the Origin and Progression of Multiple SclerosisR35NS111644 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEPHEN L HAUSER · 2019 to 2026
$9.1M
Post GWAS approach to identify cell-specific genetic pathways underlying MS riskR01NS088155 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BARANZINI, SERGIO E · 2014 to 2018
$2.2M
NINDS NIH HHS R01 NS088155NINDS NIH HHS R35 NS111644
6 · The paper itself

Abstract

Multiple sclerosis is an autoimmune disease of the CNS in which both genetic and environmental factors are involved. Genome-wide association studies revealed more than 200 risk loci, most of which harbour genes primarily expressed in immune cells. However, whether genetic differences are translated into cell-specific gene expression profiles and to what extent these are altered in patients with multiple sclerosis are still open questions in the field. To assess cell type-specific gene expression in a large cohort of patients with multiple sclerosis, we sequenced the whole transcriptome of fluorescence-activated cell sorted T cells (CD4+ and CD8+) and CD14+ monocytes from treatment-naive patients with multiple sclerosis (n = 106) and healthy subjects (n = 22). We identified 479 differentially expressed genes in CD4+ T cells, 435 in monocytes, and 54 in CD8+ T cells. Importantly, in CD4+ T cells, we discovered upregulated transcripts from the NAE1 gene, a critical subunit of the NEDD8 activating enzyme, which activates the neddylation pathway, a post-translational modification analogous to ubiquitination. Finally, we demonstrated that inhibition of NEDD8 activating enzyme using the specific inhibitor pevonedistat (MLN4924) significantly ameliorated disease severity in murine experimental autoimmune encephalomyelitis. Our findings provide novel insights into multiple sclerosis-associated gene regulation unravelling neddylation as a crucial pathway in multiple sclerosis pathogenesis with implications for the development of tailored disease-modifying agents.

Indexed as

Protein Processing, Post-TranslationalAdultCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleGene Expression ProfilingHumansLipopolysaccharide ReceptorsMaleMiddle AgedMonocytesMultiple SclerosisYoung AdultLipopolysaccharide Receptorsmultiple sclerosisneddylationtranscriptomics

Identifiers

PMID33374005
PMCPMC8491073
OpenAlexW3118151207

What OpenQuestion holds

Textmetadata
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.