Evidence map›Paper›PMID 37975799›Full record

ArticleEuropean journal of neurology2024

GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.

Qiong Liu, Juan Chen, Jin Xue, Xun Zhou, Yun Tian, Qiao Xiao, Wen Huang, Yongcheng Pan, Xiaoxia Zhou, Jian Li and 16 more

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

Article in European journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 29% 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, 6 citations in OpenAlex.

  1. Review
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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

26 authors at 1 institution in 1 country.

Qiong LiuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Juan ChenDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Jin XueCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Xun ZhouDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.ORCID 0000-0002-7325-5720
Yun TianDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
Qiao XiaoCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Wen HuangCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Yongcheng PanDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Xiaoxia ZhouDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Jian LiDepartment of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, China.
Yuwen ZhaoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Hongxu PanDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Yige WangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Runcheng HeDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Yaqin XiangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Tian TuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Qian XuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.ORCID 0000-0002-5223-9967
Qiying SunDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.ORCID 0000-0002-2031-8345
Jieqiong TanCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Xinxiang YanDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Jinchen LiCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Jifeng GuoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.ORCID 0000-0002-3658-3928
Lu ShenDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.ORCID 0000-0002-3393-8578
Ranhui DuanCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Beisha TangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Zhenhua LiuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.ORCID 0000-0003-0031-5646
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeThe role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN.

methodsA total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection.

resultsFour PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN.

conclusionsOverall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.

Indexed as

Parkinson DiseaseAnimalsDopaminergic NeuronsHumansIntercellular Signaling Peptides and ProteinsIntranuclear Inclusion BodiesMiceMice, TransgenicNerve DegenerationNerve Tissue ProteinsSubstantia NigraTrinucleotide Repeat ExpansionIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsNOTCH2NLC protein, humandopaminergic neuron degenerationGGC repeat expansionsNOTCH2NLCParkinson disease

Identifiers

PMID37975799
PMCPMC11235938
OpenAlexW4388783191

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Registered trials

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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.