Evidence map›Paper›PMID 36640336›Full record

ArticleCell reports2023

Neuronal and astrocytic contributions to Huntington's disease dissected with zinc finger protein transcriptional repressors.

Mohitkumar R Gangwani, Joselyn S Soto, Yasaman Jami-Alahmadi, Srushti Tiwari, Riki Kawaguchi, James A Wohlschlegel, Baljit S Khakh

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

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 26 citations in OpenAlex.

  1. Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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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 1 institution in 1 country.

Mohitkumar R GangwaniDepartment of Physiology, University of California Los Angeles, Los Angeles, CA 90095-1751, USA.
Joselyn S SotoDepartment of Physiology, University of California Los Angeles, Los Angeles, CA 90095-1751, USA.
Yasaman Jami-AlahmadiDepartment of Biological Chemistry, University of California Los Angeles, Los Angeles, CA 90095-1751, USA.
Srushti TiwariDepartment of Physiology, University of California Los Angeles, Los Angeles, CA 90095-1751, USA.
Riki KawaguchiCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095-1751, USA.
James A WohlschlegelDepartment of Biological Chemistry, University of California Los Angeles, Los Angeles, CA 90095-1751, USA.
Baljit S KhakhDepartment of Physiology, University of California Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, University of California Los Angeles, Los Angeles, CA 90095-1751, USA. Electronic address: bkhakh@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUSAN Y BOOKHEIMER · 2020 to 2026
$9.6M
Fundamental astrocyte biology in intact neural circuitsR35NS111583 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Baljit Khakh · 2019 to 2026
$7.9M
NICHD NIH HHS P50 HD103557NINDS NIH HHS R35 NS111583
6 · The paper itself

Abstract

Huntington's disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) resulting in expression of mutant HTT proteins (mHTT) with extended polyglutamine tracts, including in striatal neurons and astrocytes. It is unknown whether pathophysiology in vivo can be attenuated by lowering mHTT in either cell type throughout the brain, and the relative contributions of neurons and astrocytes to HD remain undefined. We use zinc finger protein (ZFP) transcriptional repressors to cell-selectively lower mHTT in vivo. Astrocytes display loss of essential functions such as cholesterol metabolism that are partly driven by greater neuronal dysfunctions, which encompass neuromodulation, synaptic, and intracellular signaling pathways. Using transcriptomics, proteomics, electrophysiology, and behavior, we dissect neuronal and astrocytic contributions to HD pathophysiology. Remarkably, brain-wide delivery of neuronal ZFPs results in strong mHTT lowering, rescue of HD-associated behavioral and molecular phenotypes, and significant extension of lifespan, findings that support translational development.

Indexed as

Huntington DiseaseAnimalsAstrocytesDisease Models, AnimalHuntingtin ProteinMutant ProteinsNeuronsTranscription FactorsZinc FingersHuntingtin ProteinMutant ProteinsTranscription FactorsastrocyteCP: NeurosciencehuntingtinHuntington’s diseasemedium spiny neuronneurodegenerationstriatumtherapeuticszinc finger protein

Identifiers

PMID36640336
PMCPMC9898160
OpenAlexW4313644061

What OpenQuestion holds

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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.