Evidence map›Paper›PMID 28973132›Full record

ArticleHuman molecular genetics2017

IKKβ and mutant huntingtin interactions regulate the expression of IL-34: implications for microglial-mediated neurodegeneration in HD.

Ali Khoshnan, Adam Sabbaugh, Barbara Calamini, Steven A Marinero, Denise E Dunn, Jung Hyun Yoo, Jan Ko, Donald C Lo, Paul H Patterson

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

Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Cell-Autonomous and Non-cell-Autonomous Pathogenic Mechanisms in Huntington's Disease: Insights from In Vitro and In Vivo Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019
    Review
  20. 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

9 authors at 2 institutions in 1 country.

Ali KhoshnanBiology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
Adam SabbaughBiology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
Barbara CalaminiDepartment of Neurobiology and Center for Drug Discovery, Duke University Medical Center, Durham, NC 27710, USA.
Steven A MarineroDepartment of Neurobiology and Center for Drug Discovery, Duke University Medical Center, Durham, NC 27710, USA.
Denise E DunnDepartment of Neurobiology and Center for Drug Discovery, Duke University Medical Center, Durham, NC 27710, USA.
Jung Hyun YooBiology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jan KoBiology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
Donald C LoDepartment of Neurobiology and Center for Drug Discovery, Duke University Medical Center, Durham, NC 27710, USA.
Paul H PattersonBiology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
California Institute of Technology · USDuke University · US

Funding

Validation of IKKbeta as a therapeutic target for HDR01NS074374 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI KHOSHNAN, ALI · 2011 to 2014
$1.4M
Novel 3D brain tissue-based screening assay for targeting microglia in CNS neurodegenerationR21NS098323 · NINDS · DUKE UNIVERSITY · PI LO, DONALD C · 2016 to 2017
$437k
NINDS NIH HHS R01 NS074374NINDS NIH HHS R21 NS098323
6 · The paper itself

Abstract

Neuronal interleukin-34 (IL-34) promotes the expansion of microglia in the central nervous system-microglial activation and expansion are in turn implicated in the pathogenesis of Huntington's disease (HD). We thus examined whether the accumulation of an amyloidogenic exon-1 fragment of mutant huntingtin (mHTTx1) modulates the expression of IL-34 in dopaminergic neurons derived from a human embryonic stem cell line. We found that mHTTx1 aggregates induce IL-34 production selectively in post-mitotic neurons. Exposure of neurons to DNA damaging agents or the excitotoxin NMDA elicited similar results suggesting that IL-34 induction may be a general response to neuronal stress including the accumulation of misfolded mHTTx1. We further determined that knockdown or blocking the activity of IκB kinase beta (IKKβ) prevented the aggregation of mHTTx1 and subsequent IL-34 production. While elevated IL-34 itself had no effect on the aggregation or the toxicity of mHTTx1 in neuronal culture, IL-34 expression in a rodent brain slice model with intact neuron-microglial networks exacerbated mHTTx1-induced degeneration of striatal medium-sized spiny neurons. Conversely, an inhibitor of the IL-34 receptor reduced microglial numbers and ameliorated mHTTx1-mediated neurodegeneration. Together, these findings uncover a novel function for IKKβ/mHTTx1 interactions in regulating IL-34 production, and implicate a role for IL-34 in non-cell-autonomous, microglial-dependent neurodegeneration in HD.

Indexed as

AnimalsCell LineCorpus StriatumExonsHumansHuntingtin ProteinHuntington DiseaseI-kappa B KinaseInterleukinsMicrogliaNeuronsNeurotoxinsPrimary Cell CultureRatsHTT protein, humanHuntingtin ProteinI-kappa B KinaseIL34 protein, humanInterleukinsNeurotoxins

Identifiers

PMID28973132
PMCPMC5886231
OpenAlexW2748316333

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.