中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (7): 1122-1128.doi: 10.4103/1673-5374.251187

• 综述:周围神经损伤修复保护与再生 • 上一篇    下一篇

以网络为中心的周围神经损伤药物:治疗整个神经保护和再生的内源性机制

  

  • 出版日期:2019-07-15 发布日期:2019-07-15

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

David Romeo-Guitart, Caty Casas   

  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
  • Online:2019-07-15 Published:2019-07-15
  • Contact: Caty Casas, PhD, Caty.Casas@uab.cat.
  • Supported by:

    This work was mainly supported by the Ministerio de Economía y Competitividad of Spain (#SAF 2014-59701) (to CC).

摘要:

orcid: 0000-0002-2273-6321 (Caty Casas)

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.

Key words: motoneuron, neurodegeneration, axonal regeneration, muscle atrophy, systems biology, neuroheal, PI3K/AKT, sirtuin 1, motor function recovery