Lunn J Simon, Hefferan Michael P, Marsala Martin, Feldman Eva L
Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Growth Factors. 2009 Jun;27(3):133-40. doi: 10.1080/08977190902814855.
Amyotrophic lateral sclerosis (ALS) is characterized by loss of both upper and lower motor neurons. ALS progression is complex and likely due to cellular dysfunction at multiple levels, including mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress, axonal dysfunction, reactive astrocytosis, and mutant superoxide dismutase expression, therefore, treatment must provide neuronal protection from multiple insults. A significant amount of ALS research focuses on growth factor-based therapies. Growth factors including insulin-like growth factor-I, vascular endothelial growth factor, brain-derived neurotrophic factor, and glial-derived neurotrophic factor exhibit robust neuroprotective effects on motor neurons in ALS models. Issues concerning growth factor delivery, stability and unwanted side effects slow the transfer of these treatments to human ALS patients. Stem cells represent a new therapeutic approach offering both cellular replacement and trophic support for the existing population. Combination therapy consisting of stem cells expressing beneficial growth factors may provide a comprehensive treatment for ALS.
肌萎缩侧索硬化症（ALS）的特征是上下运动神经元均丧失。ALS的进展很复杂，可能是由于多个层面的细胞功能障碍所致，包括线粒体功能障碍、谷氨酸兴奋性毒性、氧化应激、轴突功能障碍、反应性星形胶质细胞增生以及突变型超氧化物歧化酶的表达，因此，治疗必须为神经元提供多重损伤保护。大量的ALS研究聚焦于基于生长因子的疗法。包括胰岛素样生长因子-I、血管内皮生长因子、脑源性神经营养因子和胶质细胞源性神经营养因子在内的生长因子，在ALS模型中对运动神经元表现出强大的神经保护作用。有关生长因子递送、稳定性和不良副作用的问题减缓了这些治疗方法向人类ALS患者的转化。干细胞代表了一种新的治疗方法，可为现有细胞群体提供细胞替代和营养支持。由表达有益生长因子的干细胞组成的联合疗法可能为ALS提供全面治疗。
