The Neuroscience Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, 49100, Israel.
J Mol Neurosci. 2011 Mar;43(3):470-7. doi: 10.1007/s12031-010-9467-1. Epub 2010 Nov 7.
Amyotrophic lateral sclerosis (ALS) is a lethal disease, characterized by progressive death of motor neurons with unknown etiology. Evidence from animal models indicates that neuronal dysfunction precedes the clinical phase of the disease. However, in parallel extensive nerve sprouting and synaptic remodeling as part of a compensatory reinnervation processes and possibly also of motor neurons pathology was demonstrated. Therefore, the weakness in muscle groups will not be clinically apparent until a large proportion of motor units are lost. This motor unit loss and associated muscle function which precedes the death of motor neurons may resemble the "die-back" phenomena. Studies indicated that in the early stages the nerve terminals and motor neuron junctions are partially degraded while the cell bodies in the spinal cord are mostly intact. Treatments to rescue motor neurons according to "dying-forward" model of motor neuron pathology in ALS have shown only limited success in SOD1(G93A) transgenic mice as well as in humans. If cell body degeneration is late compared with axonal degeneration, early intervention could potentially prevent loss of motor neurons. Therefore, it should be considered, according to the dying back hypothesis, to focus on motor neurons terminals in order to delay or prevent the progressive degradation.
肌萎缩侧索硬化症（ALS）是一种致命疾病，其特征是运动神经元进行性死亡，但病因不明。动物模型的证据表明，神经元功能障碍先于疾病的临床阶段。然而，广泛的神经发芽和突触重塑作为代偿性再支配过程的一部分，以及运动神经元病理学的一部分，也得到了证实。因此，直到大量运动单位丧失，肌肉群的无力才会在临床上显现出来。这种运动单位的丧失和相关的肌肉功能，先于运动神经元的死亡，可能类似于“退行性变”现象。研究表明，在早期阶段，神经末梢和运动神经元连接处部分退化，而脊髓中的细胞体大多完好无损。根据 ALS 运动神经元病理学的“退行性变”模型，针对运动神经元的治疗方法在 SOD1(G93A)转基因小鼠以及人类中仅取得了有限的成功。如果与轴突退化相比，细胞体退化较晚，那么早期干预可能潜在地防止运动神经元的丧失。因此，根据退行性变假说，应该考虑专注于运动神经元末梢，以延迟或预防进行性退化。
