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利用人工智能揭示神经创伤的神经保护药物。

Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

机构信息

Institut de Neurociències (INc) and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB) & Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Barcelona, Spain.

Hand and Peripheral Nerve Unit, Hospital Clínic i Provincial, Universitat de Barcelona, Barcelona, Spain.

出版信息

Sci Rep. 2018 Jan 30;8(1):1879. doi: 10.1038/s41598-018-19767-3.

Abstract

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

摘要

在这里,我们采用系统生物学方法和人工智能来鉴定一种治疗周围神经根撕脱的神经保护剂。基于对根撕脱后运动神经元发生的神经退行性和神经保护过程的积累知识,我们构建了蛋白质网络,并将其转化为数学模型。我们的临床前模型中的无偏蛋白质组学数据用于机器学习算法,并对数学解决方案施加限制。解决方案使我们能够识别重新利用药物的组合作为潜在的神经保护剂,并在我们的临床前模型中对其进行验证。最好的一种名为NeuroHeal,它可以保护运动神经元,发挥抗炎作用,并促进运动功能的恢复。NeuroHeal 支持 Sirtuin 1 的激活,这对其神经保护作用至关重要。这些结果支持了以网络为中心的方法在药物发现中的价值,并证明了 NeuroHeal 作为神经创伤手术修复的辅助治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/754d/5790005/71a3ea467fb1/41598_2018_19767_Fig1_HTML.jpg

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