Evidence map›Paper›PMID 41942455›Full record

ArticleNature communications2026

ASO therapy rescues NOTCH2NLC GGC repeat expansion-induced genomic damage, 3D chromatin structural abnormalities, and senescence.

Mengjie Li, Mibo Tang, Xiaoyan Hao, Zhengwei Hu, Dongrui Ma, Shuangjie Li, Chunyan Zuo, Zhiyun Wang, Yuanyuan Liang, Yanmei Feng and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

28 authors.

Mengjie Li *Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.ORCID http://orcid.org/0000-0002-9908-0957
Mibo Tang *Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Xiaoyan HaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Zhengwei HuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Dongrui MaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Shuangjie LiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Chunyan ZuoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Zhiyun WangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Yuanyuan LiangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Yanmei FengDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Chenwei HaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Chen WangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Huanyu LiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Yalan YangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Yuemeng SunDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Shasha QiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Chengyuan MaoDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Yuming XuDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.ORCID http://orcid.org/0000-0003-2689-9897
Qun WangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
De YangDepartment of Neurology, Fuling Hospital, Chongqing University, Fuling, China.
Ruwei YangDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Ziyao ZhouDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Peilin JiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Song TanSichuan Provincial Key Laboratory for Human Disease Gene Study and Rare Disease Medical Centre and Department of Neurology, Sichuan Provincial People's Hospital, Chengdu, China.
Zaiqiang ZhangDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Hao ChenDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Albert R La SpadaDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA. alaspada@hs.uci.edu.
Changhe ShiDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China. shichanghe@gmail.com.ORCID http://orcid.org/0000-0002-4843-0072

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuronal intranuclear inclusion disease is caused by abnormal GGC repeat expansion in the NOTCH2NLC gene, though its pathogenic mechanism remains incompletely understood. This study shows that the abnormally expanded polyG-uN2C protein, encoded by the repeat sequence, contains intrinsically disordered regions and forms aggregates, leading to mislocalization of nucleophosmin and downregulation of fibrillarin. PolyG aggregates interact with nucleophosmin and rRNA, disrupting ribosomal homeostasis. Furthermore, polyG facilitates the downregulation of chromatin structural proteins CTCF and RAD21, thereby impairing chromatin organization. This pathological manifestation can be mitigated by restoring CTCF/RAD21 expression. Furthermore, in brain organoids derived from neuronal intranuclear inclusion disease patients, we observe nucleolar stress accompanied by genome-wide chromatin structural alterations. These changes correlate with increased DNA damage and cellular senescence phenotypes. Notably, antisense oligonucleotides targeting GGC effectively reduce polyG aggregation and ameliorate related molecular defects, ultimately alleviating senescence-associated phenotypes. These findings establish key mechanisms underlying neuronal intranuclear inclusion disease pathogenesis and provide proof-of-concept for targeted therapy.

Indexed as

Cellular SenescenceChromatinDNA DamageOligonucleotides, AntisenseTrinucleotide Repeat ExpansionAnimalsDNA-Binding ProteinsHumansNeuronsChromatinDNA-Binding ProteinsOligonucleotides, Antisense

Identifiers

PMID41942455
PMCPMC13233821

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