Network-centric medicine for peripheral nerve injury : treating the whole to boost endogenous mechanisms of neuroprotection and regeneration
Romeo-Guitart, David (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Casas Louzao, Caty (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Fecha:	2019
Resumen:	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.
Ayudas:	Ministerio de Economía y Competitividad SAF2014-59701
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article de revisió ; recerca ; Versió publicada
Materia:	Motoneuron ; Neurodegeneration ; Axonal regeneration ; Muscle atrophy ; Systems biology ; Neuroheal ; PI3K/AKT ; Sirtuin 1 ; Motor function recovery
Publicado en:	Neural Regeneration Research, Vol. 14 (july 2019) , p. 1122-1128, ISSN 1876-7958

DOI: 10.4103/1673-5374.251187
PMID: 30804234

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