Sendtner M
Institute for Clinical Neurobiology, University of Würzburg, Versbacherstr. 5, 97078, Würzburg, Germany,
Handb Exp Pharmacol. 2014;220:411-41. doi: 10.1007/978-3-642-45106-5_15.
Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) represent the two major forms of motoneuron disease. In both forms of disease, spinal and bulbar motoneurons become dysfunctional and degenerate. In ALS, cortical motoneurons are also affected, which contributes to the clinical phenotype. The gene defects for most familial forms of ALS and SMA have been discovered and they point to a broad spectrum of disease mechanisms, including defects in RNA processing, pathological protein aggregation, altered apoptotic signaling, and disturbed energy metabolism. Despite the fact that lack of neurotrophic factors or their corresponding receptors are not found as genetic cause of motoneuron disease, signaling pathways initiated by neurotrophic factors for motoneuron survival, axon growth, presynaptic development, and synaptic function are disturbed in ALS and SMA. Better understanding of how neurotrophic factors and downstream signaling pathways interfere with these disease mechanisms could help to develop new therapies for motoneuron disease and other neurodegenerative disorders.
肌萎缩侧索硬化症（ALS）和脊髓性肌萎缩症（SMA）是运动神经元疾病的两种主要形式。在这两种疾病形式中，脊髓和延髓运动神经元都会出现功能障碍并退化。在ALS中，皮质运动神经元也会受到影响，这导致了临床表型。大多数家族性ALS和SMA的基因缺陷已被发现，它们指向了广泛的疾病机制，包括RNA加工缺陷、病理性蛋白质聚集、凋亡信号改变和能量代谢紊乱。尽管未发现神经营养因子或其相应受体的缺乏是运动神经元疾病的遗传原因，但神经营养因子启动的用于运动神经元存活、轴突生长、突触前发育和突触功能的信号通路在ALS和SMA中受到干扰。更好地理解神经营养因子和下游信号通路如何干扰这些疾病机制，有助于开发针对运动神经元疾病和其他神经退行性疾病的新疗法。
