Evidence map›Paper›PMID 24784230›Full record

ArticleNature medicine2014

Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.

Nan Wang, Michelle Gray, Xiao-Hong Lu, Jeffrey P Cantle, Sandra M Holley, Erin Greiner, Xiaofeng Gu, Dyna Shirasaki, Carlos Cepeda, Yuqing Li and 3 more

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

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 1 pooled it
8.0field-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

104 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.

  1. Pooled it
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  8. Advancements in surgical treatments for Huntington disease: From pallidotomy to experimental therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
    Review
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44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Nan Wang1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [3].
Michelle Gray1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [3] [4].
Xiao-Hong Lu1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Jeffrey P Cantle1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Sandra M Holley1] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Erin Greiner1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [3] Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
Xiaofeng Gu1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Dyna Shirasaki1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [3] Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.
Carlos Cepeda1] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Yuqing LiDepartment of Neurology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Hongwei Dong1] Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA. [2].
Michael S Levine1] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
X William Yang1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [2] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. [3] Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
University of California, Los Angeles · USNeurobehavioral Systems · USUniversity of Florida · US

Funding

The Role of Striosome Neurons in Mediating Opiod RewardP50DA005010 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 1987 to 2021
$30.7M
Stem CellsP30HD004612 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARPENTER, ELLEN M. · 1985 to 2014
$19.5M
The Mouse Connectome Project Phase III: Assembling the global neural networks of the mouse brainR01MH094360 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DONG, HONG-WEI · 2012 to 2021
$7.4M
Transgenic Mouse Models of Huntington's DiseaseR01NS041574 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEVINE, MICHAEL S. · 2002 to 2016
$5.4M
Conditional Mouse Models: Non-cell-antonomous Toxicities in Huntington's DiseaseR01NS049501 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2004 to 2014
$3.8M
Validating NT17 Dependent Mechanisms in Huntington's Disease SuppressionR01NS074312 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2011 to 2014
$1.4M
NICHD NIH HHS P30 HD004612NIDA NIH HHS P50 DA005010NIMH NIH HHS R01 MH094360NINDS NIH HHS R01 NS041574NINDS NIH HHS R01 NS049501NINDS NIH HHS R01 NS074312NINDS NIH HHS R01 NS41574
6 · The paper itself

Abstract

Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mechanistic basis for such selective neuronal vulnerability remains unclear. A necessary step toward resolving this enigma is to define the cell types in which mHTT expression is causally linked to the disease pathogenesis. Using a conditional transgenic mouse model of HD, in which the mice express full-length human mHTT from a bacterial artificial chromosome transgene (BACHD), we genetically reduced mHTT expression in neuronal populations in the striatum, cortex or both. We show that reduction of cortical mHTT expression in BACHD mice partially improves motor and psychiatric-like behavioral deficits but does not improve neurodegeneration, whereas reduction of mHTT expression in both neuronal populations consistently ameliorates all behavioral deficits and selective brain atrophy in this HD model. Furthermore, whereas reduction of mHTT expression in cortical or striatal neurons partially ameliorates corticostriatal synaptic deficits, further restoration of striatal synaptic function can be achieved by reduction of mHTT expression in both neuronal cell types. Our study demonstrates distinct but interacting roles of cortical and striatal mHTT in HD pathogenesis and suggests that optimal HD therapeutics may require targeting mHTT in both cortical and striatal neurons.

Indexed as

AnimalsBehavioral SymptomsCorpus StriatumDisease Models, AnimalGene Expression RegulationGenetic TherapyHumansHuntingtin ProteinHuntington DiseaseMiceMotor ActivityMutationNerve Tissue ProteinsNeuronsHTT protein, humanHuntingtin ProteinNerve Tissue Proteins

Identifiers

PMID24784230
PMCPMC4067603
OpenAlexW2077225885

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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.