Evidence map›Paper›PMID 38556190›Full record

ArticleExperimental neurology2024

DDX3X overexpression decreases dipeptide repeat proteins in a mouse model of C9ORF72-ALS/FTD.

Xiujuan Fu, Zhe Zhang, Lindsey R Hayes, Noelle Wright, Julie Asbury, Shelley Li, Yingzhi Ye, Shuying Sun

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

Article in Experimental neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026
    Article
  3. Genetics in medicine open · 2026
    Article
  4. Targeting GeneInternational journal of molecular sciences · 2025
    Review
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

8 authors at 3 institutions in 1 country.

Xiujuan FuDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zhe ZhangDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lindsey R HayesBrain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Noelle WrightDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Julie AsburyNotre Dame of Maryland University, Baltimore, MD 21210, USA.
Shelley LiJohn Hopkins University, Baltimore, MD 21218, USA.
Yingzhi YeDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Physiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Shuying SunDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: shuying.sun@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USNotre Dame of Maryland University · US

Funding

Single molecule study of C9ORF72 repeat RNA metabolisms in ALS/FTDRF1NS113820 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING, WU, BIN · 2020 to 2025
$6.2M
RNA-based regulation of TDP-43 nuclear export in ALS/FTDR01NS123538 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HOKE, AHMET · 2021 to 2025
$2.4M
The role of m6A RNA methylation in C9ORF72-ALS/FTDRF1NS127925 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING · 2022 to 2024
$2.0M
Molecular mechanism of dipeptide repeat protein production from hexanucleotide repeats in C9ORF72-related ALS and FTDR01NS107347 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING · 2018 to 2022
$1.8M
Dysregulation of inhibitory synapse by poly-GR in C9ORF72-ALS/FTDR21AG072078 · NIA · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING · 2021 to 2021
$450k
NIA NIH HHS R21 AG072078NINDS NIH HHS R01 NS107347NINDS NIH HHS R01 NS123538NINDS NIH HHS RF1 NS113820NINDS NIH HHS RF1 NS127925
6 · The paper itself

Abstract

Hexanucleotide repeat expansion in C9ORF72 (C9) is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One of the proposed pathogenic mechanisms is the neurotoxicity arising from dipeptide repeat (DPR) proteins produced by repeat-associated non-AUG (RAN) translation. Therefore, reducing DPR levels emerges as a potential therapeutic strategy for C9ORF72-ALS/FTD. We previously identified an RNA helicase, DEAD-box helicase 3 X-linked (DDX3X), modulates RAN translation. DDX3X overexpression decreases poly-GP accumulation in C9ORF72-ALS/FTD patient-derived induced pluripotent stem cell (iPSC)-differentiated neurons (iPSNs) and reduces the glutamate-induced neurotoxicity. In this study, we examined the in vivo efficacy of DDX3X overexpression using a mouse model. We expressed exogenous DDX3X or GFP in the central nervous system (CNS) of the C9-500 ALS/FTD BAC transgenic or non-transgenic control mice using adeno-associated virus serotype 9 (AAV9). The DPR levels were significantly reduced in the brains of DDX3X-expressing C9-BAC mice compared to the GFP control even twelve months after virus delivery. Additionally, p62 aggregation was also decreased. No neuronal loss or neuroinflammatory response were detected in the DDX3X overexpressing C9-BAC mice. This work demonstrates that DDX3X overexpression effectively reduces DPR levels in vivo without provoking neuroinflammation or neurotoxicity, suggesting the potential of increasing DDX3X expression as a therapeutic strategy for C9ORF72-ALS/FTD.

Indexed as

Amyotrophic Lateral SclerosisC9orf72 ProteinDEAD-box RNA HelicasesDisease Models, AnimalFrontotemporal DementiaAnimalsDipeptidesDNA Repeat ExpansionHumansMaleMiceMice, TransgenicC9orf72 ProteinDdx3x protein, mouseDEAD-box RNA HelicasesDipeptidesALSC9ORF72FTDRepeat expansion

Identifiers

PMID38556190
PMCPMC11058010
OpenAlexW4393307000

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.