Abstract：
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system still lacking a cure. Treatment typically focuses on slowing the progression and managing MS symptoms. Single-cell transcriptomics allows the investigation of the immune system-the key player in MS onset and development-in great detail increasing our understanding of MS mechanisms and stimulating the discovery of the targets for potential therapies. Still, de novo drug development takes decades; however, this can be reduced by drug repositioning. A promising approach is to select potential drugs based on activated or inhibited genes and pathways. In this study, we explored the public single-cell RNA data from an experiment with six patients on single-cell RNA peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid cells (CSF) of patients with MS and idiopathic intracranial hypertension. We demonstrate that AIM2 inflammasome, SMAD2/3 signaling, and complement activation pathways are activated in MS in different CSF and PBMC immune cells. Using genes from top-activated pathways, we detected several promising small molecules to reverse MS immune cells\' transcriptomic signatures, including AG14361, FGIN-1-27, CA-074, ARP 101, Flunisolide, and JAK3 Inhibitor VI. Among these molecules, we also detected an FDA-approved MS drug Mitoxantrone, supporting the reliability of our approach.
摘要：
多发性硬化(MS)是一种尚缺乏医治办法的中枢神经体系本身免疫性疾病。治疗通常集中于减缓进展和管理MS症状。单细胞转录组学允许研究免疫系统-MS发病和发展的关键参与者-非常详细地增加我们对MS机制的理解并刺激发现潜在疗法的靶标。尽管如此，从头药物开发需要几十年；然而，这可以通过药物重新定位来减少。一种有希望的方法是基于激活或抑制的基因和途径选择潜在的药物。在这项研究中,我们从一项针对MS和特发性颅内高压患者外周血单个核细胞(PBMC)和脑脊液(CSF)的单细胞RNA实验中,探索了公开的单细胞RNA数据.我们证明AIM2炎性体，SMAD2/3信令，和补体激活途径在MS中在不同的CSF和PBMC免疫细胞中被激活。利用顶级激活途径的基因，我们检测到几种有希望的小分子逆转MS免疫细胞转录组特征，包括AG14361,FGIN-1-27,CA-074,ARP101,Funisolide,和JAK3抑制剂VI.在这些分子中，我们还检测到FDA批准的MS药物米托蒽醌，支持我们方法的可靠性。
