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Romeo-Guitart D, Casas C. Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration. Neural Regen Res. 2019;14(7):1122-1128doi: 10.4103/1673-5374.251187.
Romeo-Guitart, D., & Casas, C. (2019). Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration. Neural regeneration research, 14(7), 1122-1128. https://doi.org/10.4103/1673-5374.251187
Romeo-Guitart, David, and Casas, Caty. "Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration." Neural regeneration research vol. 14,7 (2019): 1122-1128. doi: https://doi.org/10.4103/1673-5374.251187
Romeo-Guitart D, Casas C. Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration. Neural Regen Res. 2019 Jul;14(7):1122-1128. doi: 10.4103/1673-5374.251187. PMID: 30804234; PMCID: PMC6425822.
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Neural Regen Res. 2019 Jul;14(7):1122-1128. doi: 10.4103/1673-5374.251187.

Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration.

Neural regeneration research

David Romeo-Guitart, Caty Casas

Affiliations

  1. 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.

PMID: 30804234 PMCID: PMC6425822 DOI: 10.4103/1673-5374.251187

Abstract

Peripheral nerve injuries caused by accidents may lead to paralysis, sensory disturbances, anaesthesia, and lack of autonomic functions. Functional recovery after disconnection of the motoneuronal soma from target tissue with proximal rupture of axons is determined by several factors: motoneuronal soma viability, proper axonal sprouting across inhibitory zones and elongation toward specific muscle, effective synapse contact rebuilding, and prevention of muscle atrophy. Therapies, such as adjuvant drugs with pleiotropic effects, that promote functional recovery after peripheral nerve injury are needed. Toward this aim, we designed a drug discovery workflow based on a network-centric molecular vision using unbiased proteomic data and neural artificial computational tools. Our focus is on boosting intrinsic capabilities of neurons for neuroprotection; this is in contrast to the common approach based on suppression of a pathobiological pathway known to be associated with disease condition. Using our workflow, we discovered neuroheal, a combination of two repurposed drugs that promotes motoneuronal soma neuroprotection, is anti-inflammatory, enhances axonal regeneration after axotomy, and reduces muscle atrophy. This drug discovery workflow has thus yielded a therapy that is close to its clinical application.

Keywords: PI3K/AKT; axonal regeneration; motoneuron; motor function recovery; muscle atrophy; neurodegeneration; neuroheal; sirtuin 1; systems biology

Conflict of interest statement

None

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