Krakora Dan, Macrander Corey, Suzuki Masatoshi
Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
Neurol Res Int. 2012;2012:379657. doi: 10.1155/2012/379657. Epub 2012 Aug 7.
Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by the progressive degeneration of upper and lower motor neurons (MNs), leading to muscular atrophy and eventual respiratory failure. ALS research has primarily focused on mechanisms regarding MN cell death; however, degenerative processes in the skeletal muscle, particularly involving neuromuscular junctions (NMJs), are observed in the early stages of and throughout disease progression. According to the "dying-back" hypothesis, NMJ degeneration may not only precede, but actively cause upper and lower MN loss. The importance of NMJ pathology has relatively received little attention in ALS, possibly because compensatory mechanisms mask NMJ loss for prolonged periods. Many mechanisms explaining NMJ degeneration have been proposed such as the disruption of anterograde/retrograde axonal transport, irregular cellular metabolism, and changes in muscle gene and protein expression. Neurotrophic factors, which are known to have neuroprotective and regenerative properties, have been intensely investigated for their therapeutic potential in both the preclinical and clinical setting. Additional research should focus on the potential of preserving NMJs in order to delay or prevent disease progression.
肌萎缩侧索硬化症（ALS）是一种神经肌肉疾病，其特征是上下运动神经元（MNs）进行性退化，导致肌肉萎缩并最终呼吸衰竭。ALS研究主要集中在MN细胞死亡的机制上；然而，在疾病进展的早期阶段及整个过程中，均可观察到骨骼肌的退化过程，尤其是涉及神经肌肉接头（NMJs）的退化。根据“回返性死亡”假说，NMJ退化不仅可能先于上下MN丢失，而且还会主动导致其丢失。NMJ病理学的重要性在ALS中相对较少受到关注，可能是因为补偿机制长时间掩盖了NMJ的丢失。已经提出了许多解释NMJ退化的机制，例如顺行/逆行轴突运输的破坏、不规则的细胞代谢以及肌肉基因和蛋白质表达的变化。已知具有神经保护和再生特性的神经营养因子，已在临床前和临床环境中对其治疗潜力进行了深入研究。进一步的研究应关注保留NMJ的潜力，以延缓或预防疾病进展。
