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构建 miRNA 调控的药物-通路网络筛选多发性硬化症的药物再利用候选物。

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis.

机构信息

Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China,Department of Neurology, Peking UnionMedical College Hospital, Beijing 100730, China.

出版信息

Medicine (Baltimore). 2022 Mar 18;101(11). doi: 10.1097/MD.0000000000029107.

DOI:10.1097/MD.0000000000029107
PMID:35356949
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10684250/
Abstract

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

鉴于多发性硬化症(MS)的高残疾率,需要更安全、更有效的治疗药物。现有文献强调了 miRNA 在 MS 病理生理学中的重要作用。然而,很少有研究通过潜在的 miRNA 调节能力探索现有药物在治疗 MS 中的用途。本研究确定了由于其各自的 miRNA 关联而可能加剧 MS 风险的基因。然后,通过基于基因的 miRNA 调节药物途径网络的构建,确定了潜在的药物候选物。我们总共发现了 48 个 MS 风险途径、133 个 MS 风险 miRNA 和 186 种可影响这些途径的药物。受治疗候选物调节的潜在 MS 风险 miRNA 为 hsa05215 和 hsa05152。我们通过分析基于基因的 miRNA 调节药物途径网络的特性,并通过评估各自的 Z 值来发现一些新的 MS 药物,来分析 miRNA 调节药物途径网络的特性。总共确定了 20 种可能的药物候选物,包括人免疫球蛋白、阿司匹林、阿仑单抗、米诺环素、阿昔单抗、阿莱夫西普、帕利珠单抗、贝伐单抗、依那西普、托西莫单抗、米诺环素、依那西普、卡妥索单抗和沙利鲁单抗。然后,针对每种药物在治疗 MS 中的可能作用机制对其进行了探讨。本研究为 MS 的生物学机制以及可能的治疗策略提供了新的视角。

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Multiple sclerosis is linked to MAPK overactivity in microglia.多发性硬化症与小胶质细胞中 MAPK 的过度活跃有关。
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