Coleman Michael
The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.
Nat Rev Neurosci. 2005 Nov;6(11):889-98. doi: 10.1038/nrn1788.
A wide range of insults can trigger axon degeneration, and axons respond with diverse morphology, topology and speed. However, recent genetic, immunochemical, morphological and pharmacological investigations point to convergent degeneration mechanisms. The principal convergence points - poor axonal transport, mitochondrial dysfunction and an increase in intra-axonal calcium - have been identified by rescuing axons with the slow Wallerian degeneration gene (Wld(S)) and studies with blockers of sodium or calcium influx. By understanding how the pathways fit together, we can combine our knowledge of mechanisms, and potentially also treatment strategies, from different axonal disorders.
多种损伤均可引发轴突退变,轴突则会以多样的形态、拓扑结构和速度做出反应。然而,近期的遗传学、免疫化学、形态学及药理学研究表明,存在趋同的退变机制。通过利用慢 Wallerian 退变基因(Wld(S))拯救轴突以及使用钠或钙内流阻滞剂进行研究,已确定了主要的趋同点——轴突运输功能不良、线粒体功能障碍以及轴突内钙含量增加。通过了解这些途径如何相互关联,我们能够整合来自不同轴突疾病的机制知识以及潜在的治疗策略。