Novel Insights Into the Association Between Parkinson's Disease and Constipation: Role of SHMT2 as a Promising Biomarker.

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2026-05-01 DOI:10.1002/cns.70912

Jiehua Su, Kaixun Huang, Xiuna Jing, Xiaohuan Liu, Cheng Wen, Rulin Geng, Zhuoying Lai, Zhijia Ruan, Yiqiang Zhan, Danyu Lin, Enxiang Tao

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引用次数: 0

Abstract

Aims: We aimed to investigate the shared molecular pathways between Parkinson's disease (PD) and constipation using bioinformatics analysis.

Methods: Differentially expressed genes (DEGs) were identified via the R limma package, and Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify hub modules. Biological enrichment analysis clarified the biological processes involved. A gene-gene interaction (GGI) network was constructed to identify shared hub biomarkers. Validation of these biomarkers was done in vitro with α-synuclein (α-syn)-treated SH-SY5Y cells and in vivo through α-syn-induced PD mouse models, A53T transgenic mice, and loperamide-induced constipation models.

Results: Numerous DEGs were identified in both conditions, with 14 shared DEGs found through the intersection of core modules and upregulated DEGs. These DEGs are primarily involved in energy metabolism, protein modification, and mitochondrial function. Five key hub genes were identified using the GGI network and gene topological analysis. Notably, Serine hydroxymethyltransferase 2 (SHMT2) expression was significantly upregulated after α-syn treatment in vitro. Immunohistochemical and immunofluorescence analyses revealed elevated SHMT2 expression in brain and colon tissues in PD mouse models (p < 0.001), whereas in constipation models, SHMT2 was only elevated in the colon wall with no significant expression in the enteric nervous system.

Conclusion: Our findings offer new views on the molecular link between PD and constipation, suggesting SHMT2 as a possible biomarker and therapeutic target for PD symptoms.

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帕金森病和便秘之间关联的新见解：SHMT2作为一种有前景的生物标志物的作用

目的：我们旨在利用生物信息学分析研究帕金森病（PD）和便秘之间的共同分子通路。方法：通过R limma软件包鉴定差异表达基因（deg），并进行加权基因共表达网络分析（WGCNA）鉴定轮毂模块。生物富集分析阐明了所涉及的生物过程。构建基因-基因互作（GGI）网络，识别共享枢纽生物标志物。在体外用α-突触核蛋白（α-syn）处理的SH-SY5Y细胞，在体内用α-syn诱导的PD小鼠模型、A53T转基因小鼠和洛哌丁胺诱导的便秘模型对这些生物标志物进行验证。结果：在两种情况下都鉴定出了大量的deg，通过核心模块和上调的deg的交集发现了14个共享的deg。这些deg主要参与能量代谢、蛋白质修饰和线粒体功能。利用GGI网络和基因拓扑分析鉴定出5个关键枢纽基因。值得注意的是，α-syn处理后，丝氨酸羟甲基转移酶2 （SHMT2）的表达显著上调。免疫组织化学和免疫荧光分析显示，PD小鼠模型中SHMT2在脑和结肠组织中的表达升高(p)。结论：我们的研究结果为PD与便秘之间的分子联系提供了新的观点，提示SHMT2可能是PD症状的生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.