TY - JOUR
T1 - Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence
AU - Romeo-Guitart, David
AU - Forés, Joaquim
AU - Herrando-Grabulosa, Mireia
AU - Valls, Raquel
AU - Leiva-Rodríguez, Tatiana
AU - Galea, Elena
AU - González-Pérez, Francisco
AU - Navarro, Xavier
AU - Petegnief, Valerie
AU - Bosch, Assumpció
AU - Coma, Mireia
AU - Mas, José Manuel
AU - Casas, Caty
PY - 2018/12/1
Y1 - 2018/12/1
N2 - © 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.
AB - © 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.
U2 - 10.1038/s41598-018-19767-3
DO - 10.1038/s41598-018-19767-3
M3 - Article
C2 - 29382857
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 1879
ER -