背景:神经递质转运障碍可能在帕金森病(PD)中起关键作用,和溶质载体家族6成员12(SLC6A12)编码神经递质转运蛋白。然而,SLC6A12和PD之间的关系仍未被探索。
方法:我们利用GEO数据库(107个样本)和临床数据(80个样本)通过差异表达分析研究SLC6A12在PD中的作用,ROC分析,和RT-qPCR实验。随后,体外模型,轴突长度测量,CCK8测定,流式细胞术,和JC-1测定进行。此外,基因本体论(GO),京都基因和基因组百科全书(KEGG)分析,蛋白质-蛋白质相互作用(PPI)网络,基因集富集分析(GSEA),和蛋白质印迹实验进行评估,以探索SLC6A12在PD中的功能和机制途径。最后,进行CIBERSORT分析以研究SLC6A12与PD中免疫细胞之间的相关性。
结果:与健康对照组相比,PD患者中SLC6A12的表达明显更高。在PD模型中抑制SLC6A12表达可增强神经元生长和增殖活性,同时减少细胞凋亡。此外,SLC6A12被发现参与神经元发育,突触功能,和PD中的神经蛋白转运过程,可能通过Ras/Raf/MEK/ERK轴调节MAPK信号通路,有助于PD的病理过程。此外,SLC6A12与PD的免疫环境紊乱有关,显著影响CD4T细胞表达。
结论:本研究首次记录了SLC6A12在PD中的致病性,扩大了对其分子功能的理解,并为PD的精确治疗提供了潜在的靶标。
BACKGROUND: Neurotransmitter transport disorders may play a crucial role in Parkinson\'s Disease (PD), and Solute carrier family 6 member 12 (
SLC6A12) encodes a neurotransmitter transporter. However, the relationship between
SLC6A12 and PD remains largely unexplored.
METHODS: We utilized the GEO database (107 samples) and clinical data (80 samples) to investigate the role of SLC6A12 in PD through differential expression analysis, ROC analysis, and RT-qPCR experiments. Subsequently, in vitro model, axon length measurement, CCK8 assay, flow cytometry, and JC-1 assays were conducted. Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and western blot experiments were assessed to explore the functional and mechanistic pathways of SLC6A12 in PD. Finally, CIBERSORT analysis was performed to investigate the correlation between SLC6A12 and immune cells in PD.
RESULTS: The expression of
SLC6A12 was significantly higher in individuals with PD compared to healthy controls. Inhibiting
SLC6A12 expression in PD models enhanced neuronal growth and proliferation activity while reducing cell apoptosis. Furthermore,
SLC6A12 was found to be involved in neuronal development, synaptic function, and neural protein transport processes in PD, potentially regulating the MAPK signaling pathway through the Ras/Raf/MEK/ERK axis, contributing to the pathological process of PD. Additionally, SLC6A12 was implicated in immune environment disturbances in PD, notably affecting CD4 T cell expression.
CONCLUSIONS: This study documented the pathogenicity of SLC6A12 in PD for the first time, expanding the understanding of its molecular function and providing a potential target for precise treatment of PD.