PDF(Pubmed)
Abstract：
UNASSIGNED: Given the high disability rate of multiple sclerosis (MS), there is a need for safer and more effective therapeutic agents. Existing literature highlights the prominent roles of miRNA in MS pathophysiology. Nevertheless, there are few studies that have explored the usefulness of existing drugs in treating MS through potential miRNA-modulating abilities.The current investigation identifies genes that may exacerbate the risk of MS due to their respective miRNA associations. These findings were then used to determine potential drug candidates through the construction of miRNA-regulated drug-pathway network through genes. We uncovered a total of 48 MS risk pathways, 133 MS risk miRNAs, and 186 drugs that can affect these pathways. Potential MS risk miRNAs that are also regulated by therapeutic candidates were hsa05215 and hsa05152. We analyzed the properties of the miRNA-regulated drug-pathway network through genes and uncovered a number of novel MS agents by assessing their respective Z-values.A total of 20 likely drug candidates were identified, including human immunoglobulin, aspirin, alemtuzumab, minocycline, abciximab, alefacept, palivizumab, bevacizumab, efalizumab, tositumomab, minocycline, etanercept, catumaxomab, and sarilumab. Each of these agents were then explored with regards to their likely mechanism of action in treating MS.The current investigation provides a fresh perspective on MS biological mechanisms as well as likely treatment strategies.
摘要：
未经授权：鉴于多发性硬化症（MS）的高致残率，需要更安全和更有效的治疗剂。现有文献强调miRNA在MS病理生理学中的重要作用。然而，很少有研究探索现有药物通过潜在的miRNA调节能力治疗MS的有效性。当前的研究鉴定了由于其各自的miRNA关联而可能加剧MS风险的基因。这些发现然后用于通过构建通过基因的miRNA调节的药物途径网络来确定潜在的候选药物。我们发现了总共48个MS风险通路，133个MS风险miRNA，和186种可以影响这些途径的药物。也受治疗候选物调节的潜在MS风险miRNA是hsa05215和hsa05152。我们通过基因分析了miRNA调节的药物途径网络的特性，并通过评估其各自的Z值发现了许多新的MS试剂。总共确定了20种可能的候选药物，包括人类免疫球蛋白，阿司匹林,阿仑单抗，米诺环素,阿昔单抗,alefacept,帕利珠单抗,贝伐单抗,efalizumab,Tositumomab,米诺环素,依那西普,Catumaxomab,还有sarilumab.然后探索这些药物中的每一种治疗MS的可能作用机制。当前的研究为MS生物学机制以及可能的治疗策略提供了新的视角。
