Pollari Eveliina, Goldsteins Gundars, Bart Geneviève, Koistinaho Jari, Giniatullin Rashid
Molecular Brain Research Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland ; Experimental Neurology - Laboratory of Neurobiology, Department of Neurosciences, Vesalius Research Center, KULeuven - University of Leuven Leuven, Belgium.
Molecular Brain Research Laboratory, Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finland.
Front Cell Neurosci. 2014 May 13;8:131. doi: 10.3389/fncel.2014.00131. eCollection 2014.
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motoneurons and degradation of the neuromuscular junctions (NMJ). Consistent with the dying-back hypothesis of motoneuron degeneration the decline in synaptic function initiates from the presynaptic terminals in ALS. Oxidative stress is a major contributory factor to ALS pathology and affects the presynaptic transmitter releasing machinery. Indeed, in ALS mouse models nerve terminals are sensitive to reactive oxygen species (ROS) suggesting that oxidative stress, along with compromised mitochondria and increased intracellular Ca(2+) amplifies the presynaptic decline in NMJ. This initial dysfunction is followed by a neurodegeneration induced by inflammatory agents and loss of trophic support. To develop effective therapeutic approaches against ALS, it is important to identify the mechanisms underlying the initial pathological events. Given the role of oxidative stress in ALS, targeted antioxidant treatments could be a promising therapeutic approach. However, the complex nature of ALS and failure of monotherapies suggest that an antioxidant therapy should be accompanied by anti-inflammatory interventions to enhance the restoration of the redox balance.
肌萎缩侧索硬化症（ALS）的特征是运动神经元进行性丧失以及神经肌肉接头（NMJ）退化。与运动神经元退化的回返性死亡假说一致，ALS中突触功能的下降始于突触前终末。氧化应激是ALS病理的一个主要促成因素，并影响突触前递质释放机制。事实上，在ALS小鼠模型中，神经终末对活性氧（ROS）敏感，这表明氧化应激与线粒体功能受损和细胞内Ca(2+)增加一起，加剧了NMJ的突触前功能衰退。这种初始功能障碍随后是由炎症因子诱导的神经退行性变和营养支持的丧失。为了开发针对ALS的有效治疗方法，识别初始病理事件背后的机制很重要。鉴于氧化应激在ALS中的作用，靶向抗氧化治疗可能是一种有前景的治疗方法。然而，ALS的复杂性和单一疗法的失败表明，抗氧化治疗应辅以抗炎干预，以增强氧化还原平衡的恢复。
