Zhang Moxuan, Meng Wenjia, Liu Chong, Wang Huizhi, Li Renpeng, Wang Qiao, Gao Yuan, Zhou Siyu, Du Tingting, Yuan Tianshuo, Shi Lin, Han Chunlei, Meng Fangang
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Brain Sci. 2023 Jun 30;13(7):1015. doi: 10.3390/brainsci13071015.
Parkinson's disease (PD) is the second most common neurodegenerative disease; it mainly occurs in the elderly population. Cuproptosis is a newly discovered form of regulated cell death involved in the progression of various diseases. Combining multiple GEO datasets, we analyzed the expression profile and immunity of cuproptosis-related genes (CRGs) in PD. Dysregulated CRGs and differential immune responses were identified between PD and non-PD substantia nigra. Two CRG clusters were defined in PD. Immune analysis suggested that CRG cluster 1 was characterized by a high immune response. The enrichment analysis showed that CRG cluster 1 was significantly enriched in immune activation pathways, such as the Notch pathway and the JAK-STAT pathway. KIAA0319, AGTR1, and SLC18A2 were selected as core genes based on the LASSO analysis. We built a nomogram that can predict the occurrence of PD based on the core genes. Further analysis found that the core genes were significantly correlated with tyrosine hydroxylase activity. This study systematically evaluated the relationship between cuproptosis and PD and established a predictive model for assessing the risk of cuproptosis subtypes and the outcome of PD patients. This study provides a new understanding of PD-related molecular mechanisms and provides new insights into the treatment of PD.
帕金森病（PD）是第二常见的神经退行性疾病；主要发生在老年人群中。铜死亡是一种新发现的受调控的细胞死亡形式，与多种疾病的进展有关。结合多个基因表达综合数据库（GEO）数据集，我们分析了帕金森病中铜死亡相关基因（CRGs）的表达谱和免疫情况。在帕金森病和非帕金森病黑质之间鉴定出CRGs失调和免疫反应差异。在帕金森病中定义了两个CRG簇。免疫分析表明，CRG簇1的特征是免疫反应高。富集分析表明，CRG簇1在免疫激活途径中显著富集，如Notch途径和JAK-STAT途径。基于套索分析选择KIAA0319、AGTR1和SLC18A2作为核心基因。我们构建了一个基于核心基因预测帕金森病发生的列线图。进一步分析发现，核心基因与酪氨酸羟化酶活性显著相关。本研究系统评估了铜死亡与帕金森病之间的关系，并建立了一个评估铜死亡亚型风险和帕金森病患者预后的预测模型。本研究为帕金森病相关分子机制提供了新的认识，并为帕金森病的治疗提供了新的见解。
