Evidence map›Paper›PMID 39354865›Full record

ArticleCNS neuroscience & therapeutics2024

Genetic Analysis of Neurite Outgrowth Inhibitor-Associated Genes in Parkinson's Disease: A Cross-Sectional Cohort Study.

Xiurong Huang, Yige Wang, Yaqin Xiang, Yuwen Zhao, Hongxu Pan, Zhenhua Liu, Qian Xu, Qiying Sun, Jieqiong Tan, Xinxiang Yan and 3 more

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Xiurong HuangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yige WangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yaqin XiangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yuwen ZhaoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hongxu PanDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhenhua LiuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0002-9957-0956
Qian XuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0002-5223-9967
Qiying SunDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0002-2031-8345
Jieqiong TanCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Xinxiang YanDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jinchen LiDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Beisha TangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jifeng GuoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Funding

National Key Plan for Scientific Research and Development of China 2021YFC2501204National Key Research and Development Program of China 2021YFC2502100National Natural Science Foundation of China 82071439National Natural Science Foundation of China 82271281Technology Major Project of Hunan Provincial Science and Technology Department 2021SK1010
6 · The paper itself

Abstract

backgroundParkinson's disease (PD) is a neurodegenerative disease caused by a combination of aging, environmental, and genetic factors. Previous research has implicated both causative and susceptibility genes in PD development. Nogo-A, a neurite outgrowth inhibitor, has been shown to impact axon growth through ligand-receptor interactions negatively, thereby involved in the deterioration of dopaminergic neurons. However, rare genetic studies have identified the relationship between neurite outgrowth inhibitor (Nogo)-associated genes and PD from a signaling pathway perspective.

methodsWe enrolled 3959 PD patients and 2931 healthy controls, categorized into two cohorts based on their family history and age at onset: sporadic early Parkinson's disease & familial Parkinson's disease (sEOPD & FPD) cohort and sporadic late Parkinson's disease (sLOPD) cohort. We selected 17 Nogo-associated genes and stratified them into three groups via their function, respectively, ligand, receptors, and signaling pathway groups. Additionally, we conducted the burden analysis in rare variants, the logistic regression analysis in common variants, and the genotype-phenotype association analysis. Last, bioinformatics analysis and functional experiments were conducted to identify the role of the MTOR gene in PD.

resultsOur findings demonstrated that the missense variants in the MTOR gene might increase PD risk, while the deleterious variants in the receptor subtype of Nogo-associated genes might mitigate PD risk. However, common variants of Nogo-associated genes showed no association with PD development in two cohorts. Furthermore, genotype-phenotype association analysis suggested that PD patients with MTOR gene variants exhibited relatively milder motor symptoms but were more susceptible developing dyskinesia. Additionally, bioinformatics analysis results showed MTOR gene was significantly decreased in PD, indicating a potential negative role of the mTOR in PD pathogenesis. Experimental data further demonstrated that MHY1485, a mTOR agonist, could rescue MPP

conclusionsOur preliminary investigation highlights the association of Nogo-associated genes with PD onset in the Chinese mainland population and hints at the potential role of the MTOR gene in PD. Further research is warranted to elucidate the mechanistic pathways underlying these associations and their therapeutic implications.

Indexed as

Nogo ProteinsParkinson DiseaseAgedCohort StudiesCross-Sectional StudiesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleMiddle AgedTOR Serine-Threonine KinasesMTOR protein, humanNogo ProteinsTOR Serine-Threonine Kinasesaxon growthgenotype–phenotype associationneurite outgrowth inhibitor‐associated genesParkinson's diseaserare variant

Identifiers

PMID39354865
PMCPMC11445604

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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.