球形细胞脑白质营养不良（Globoid Cell Leukodystrophy，GLD），也被称为克拉伯病（Krabbe disease，KD），是一种罕见的遗传性神经退行性疾病。该病的成因是由于溶酶体酶GALC的缺乏所导致。在GLD患者的免疫系统中，细胞因子的异常表达可能与疾病发病机制中的免疫失衡有着密切的联系。本研究的主要目的是基于实验室之前的GLD-NSC转录组数据，来识别GLD中的关键免疫相关基因以及潜在的药物候选物。

本研究采用了GEO数据库的GEO2R工具和Sangerbox平台对GLD-NSCs（GSE212512）的转录组数据进行了深入分析。通过多种生物信息学方法，鉴定出了与免疫反应相关的差异表达基因（Differentially expressed genes,DEGs）。然后利用DAVID数据库进行了功能富集分析和通路分析，以揭示这些基因在生物学过程中的潜在作用。此外，使用了STRING数据库和Cytoscape软件构建并分析了蛋白质-蛋白质相互作用(Protein-protein interaction,PPI)网络。通过Cytoscape软件插件的拓扑分析，确定了GLD关键的免疫相关基因。为了寻找潜在的对应治疗药物，利用DGIdb和DrugMAP数据库进行了筛选，并使用CB-DOCK2软件进行了分子对接实验验证。

在GLD-NSCs中，成功鉴定出了61个与免疫相关的差异表达基因，确定了GDNF、EGF、KDR、FGF10和MET这五个基因为关键免疫相关基因。通过进一步药物筛选，我们发现了一些对这些关键基因具有高结合亲和力的药物候选物，包括针对GDNF的Gentamicin、针对EGF的 Cetuximab、针对KDR的Tivozanib和针对MET的Capmatinib。

本研究对GLD中免疫相关基因进行了分析，并成功确定了潜在的免疫治疗靶点和药物候选物。这些研究结果不仅加深了对GLD的理解，而且可能为未来关于这一罕见疾病的诊断、治疗和预后研究提供重要的指导和参考。

Globoid Cell Leukodystrophy (GLD), also known as Krabbe disease (KD), is a rare inherited neurodegenerative disorder. The disease is caused by a deficiency of the lysosomal enzyme GALC. In the immune system of GLD patients, abnormal cytokine expression may be closely linked to immune dysregulation in the disease pathogenesis. The primary objective of this study is to identify key immune-related genes and potential drug candidates in GLD based on previous laboratory transcriptomic data of GLD-NSCs.

This study conducted an in-depth analysis of transcriptomic data from GLD-NSCs (GSE212512) using the GEO2R tool from the GEO database and the Sangerbox platform. Through multiple bioinformatics approaches, differentially expressed genes (DEGs) associated with immune responses were identified. Functional enrichment and pathway analyses were then performed using the DAVID database to elucidate the potential roles of these genes in biological processes. Additionally, the STRING database and Cytoscape software were employed to construct and analyze a protein-protein interaction (PPI) network. Topological analysis via Cytoscape plugins identified critical immune-related genes in GLD. To explore potential therapeutic agents, screening was conducted using the DGIdb and DrugMAP databases, followed by molecular docking validation with CB-DOCK2 software.

In GLD-NSCs, 61 immune-related DEGs were successfully identified, with five genes—GDNF, EGF, KDR, FGF10, and MET—determined as key immune-related genes. Further drug screening revealed several high-affinity drug candidates targeting these key genes, including Gentamicin for GDNF, Cetuximab for EGF, Tivozanib for KDR, and Capmatinib for MET.

This study analyzed immune-related genes in GLD and successfully identified potential immunotherapeutic targets and drug candidates. These findings not only enhance the understanding of GLD but may also provide critical guidance and references for future research on the diagnosis, treatment, and prognosis of this rare disease.