Department of Neurology, Science and Technology Innovation Park of the Fourth Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province 150028, China.
Department of Neurology, Science and Technology Innovation Park of the Fourth Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province 150028, China.
Neurosci Lett. 2024 Jan 1;818:137564. doi: 10.1016/j.neulet.2023.137564. Epub 2023 Nov 25.
β-Amyloid (Aβ) induced neurotoxicity is an implicated mechanism in Alzheimer's disease (AD). This study focused on the role of GDP dissociation inhibitor 1 (GDI1) in Aβ-induced neurotoxicity.
Data from the GEO database for AD-related datasets GSE140829, GSE63061, GSE36980, and GSE60360 were downloaded and identified common differentially expressed genes (coDEGs). The mRNA levels of GDI1 in the serum of AD patients were analyzed by RT-qPCR. ROC curve evaluated the diagnostic value. Aβ25-35 induced SH-SY5Y cells to construct an AD cell model. CCK-8, flow cytometry, and ELISA assay were used to analyze cell viability, apoptosis, and concentrations of inflammatory factors. KEGG enrichment was employed to analyze the signal pathway of targets from GDI1 in the AD.
The GEO database identifies coDEGs including GDI1. GDI1 is generally elevated in serum from AD patients as well as in Aβ-induced SH-SY5Y cells. GDI1 has 77.97% sensitivity and 84.44% specificity to identify AD patients from controls. Aβ induced decreased cell viability, increased apoptosis, and promoted over-secretion of inflammatory cytokines, but they were all partially weakened by reduced GDI1. What's more, the GDI1 interacting gene and AD target gene were co-enriched on Endocytosis and MAPK signaling pathway.
Elevated GDI1 is a potential diagnostic biomarker for AD and that inhibition of GDI1 attenuates Aβ-induced neurotoxicity in AD. Our study offers new horizons for AD treatment.
β-淀粉样蛋白（Aβ）诱导的神经毒性是阿尔茨海默病（AD）的一种发病机制。本研究重点探讨 GDP 解离抑制剂 1（GDI1）在 Aβ 诱导的神经毒性中的作用。
从 AD 相关数据集 GEO 数据库中下载 GSE140829、GSE63061、GSE36980 和 GSE60360 数据，识别共同差异表达基因（coDEGs）。采用 RT-qPCR 分析 AD 患者血清中 GDI1 的 mRNA 水平。ROC 曲线评估诊断价值。Aβ25-35 诱导 SH-SY5Y 细胞构建 AD 细胞模型。CCK-8、流式细胞术和 ELISA 检测分析细胞活力、细胞凋亡和炎症因子浓度。KEGG 富集分析用于分析 GDI1 在 AD 中的靶标信号通路。
GEO 数据库鉴定出包括 GDI1 在内的 coDEGs。AD 患者血清和 Aβ 诱导的 SH-SY5Y 细胞中 GDI1 普遍升高。GDI1 对 AD 患者和对照的识别具有 77.97%的灵敏度和 84.44%的特异性。Aβ 诱导细胞活力降低、凋亡增加和炎症因子过度分泌，但通过降低 GDI1，这些变化均部分减弱。此外，GDI1 相互作用基因和 AD 靶基因在内吞作用和 MAPK 信号通路中共同富集。
升高的 GDI1 是 AD 的潜在诊断生物标志物，抑制 GDI1 可减轻 AD 中 Aβ 诱导的神经毒性。本研究为 AD 的治疗提供了新的思路。
