National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University), The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, China.
College of Urban and Environmental Sciences, Northwest University, Xi'an, China.
Mol Neurobiol. 2024 Sep;61(9):6920-6933. doi: 10.1007/s12035-024-03996-x. Epub 2024 Feb 16.
Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the potential role of autophagy-related genes in MS diseases by using bioinformatics combined with machine learning methods. Finally, we obtained 9 autophagy genes with the highest correlation with MS, and further changes in these autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of great significance for the further exploration of autophagy-related genes in demyelinating diseases.
多发性硬化症（MS）是中青年人群慢性神经功能障碍的主要原因，影响全球约 250 万人。其特征为炎症、多灶性脱髓鞘、轴突丢失以及白质和灰质胶质增生。自噬是一种高度保守的蛋白质降解途径。自噬相关基因的多态性与多种自身免疫性疾病有关，包括系统性红斑狼疮、类风湿关节炎、银屑病和多发性硬化症。然而，自噬在多发性硬化症中的意义仍有待阐明。本文旨在通过生物信息学结合机器学习方法，探讨自噬相关基因在多发性硬化症中的潜在作用。最后，我们获得了 9 个与多发性硬化症相关性最高的自噬基因，并在实验性自身免疫性脑脊髓炎（EAE）模型和吞噬髓鞘碎片（MD）的少突胶质前体细胞（OPC）中进一步验证了这些自噬基因的变化。结合生物信息学分析和实验数据，发现 Becn1 表现出明显的表达异常，表明该基因在自噬和 OPC 吞噬 MD 中具有重要功能。这项工作对于进一步探索脱髓鞘疾病中的自噬相关基因具有重要意义。
