Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

David Romeo-Guitart, Joaquim Forés, Mireia Herrando-Grabulosa, Raquel Valls, Tatiana Leiva-Rodríguez, Elena Galea, Francisco González-Pérez, Xavier Navarro, Valerie Petegnief, Assumpció Bosch, Mireia Coma, José Manuel Mas, Caty Casas

Producció científica: Contribució a revistaArticleRecerca

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Resum

© 2018 The Author(s). 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.
Idioma originalAnglès
Número d’article1879
RevistaScientific Reports
Volum8
Número1
DOIs
Estat de la publicacióPublicada - 1 de des. 2018

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