PDF(Pubmed)
Abstract：
Muscular dystrophies are a devastating class of diseases that result in a progressive loss of muscle integrity. Duchenne Muscular Dystrophy, the most prevalent form of Muscular Dystrophy, is due to the loss of functional Dystrophin. While much is known regarding destruction of muscle tissue in these diseases, much less is known regarding the synaptic defects that also occur in these diseases. Synaptic defects are also among the earliest hallmarks of neurodegenerative diseases, including the neuromuscular disease Amyotrophic Lateral Sclerosis (ALS). Our current study investigates synaptic defects within adult muscle tissues as well as presynaptic motor neurons in Drosophila dystrophin mutants. Here we demonstrate that the progressive, age-dependent loss of flight ability in dystrophin mutants is accompanied by disorganization of Neuromuscular Junctions (NMJs), including impaired localization of both presynaptic and postsynaptic markers. We show that these synaptic defects, including presynaptic defects within motor neurons, are due to the loss of Dystrophin specifically within muscles. These results should help to better understand the early synaptic defects preceding cell loss in neuromuscular disorders.
摘要：
肌营养不良是导致肌肉完整性进行性丧失的一类破坏性疾病。杜氏肌营养不良症,最常见的肌肉萎缩症,是由于功能性肌营养不良蛋白的丧失。虽然人们对这些疾病中肌肉组织的破坏有很多了解，对于这些疾病中也发生的突触缺陷，人们知之甚少。突触缺陷也是神经退行性疾病的最早标志之一，包括神经肌肉疾病肌萎缩侧索硬化症（ALS）。我们目前的研究调查了成年肌肉组织中的突触缺陷以及果蝇肌营养不良蛋白突变体中的突触前运动神经元。在这里，我们证明了进步，肌营养不良蛋白突变体的飞行能力的年龄依赖性丧失伴随着神经肌肉结（NMJs）的紊乱，包括突触前和突触后标记的定位受损。我们发现这些突触缺陷,包括运动神经元内的突触前缺陷，是由于肌肉内的肌营养不良蛋白的损失。这些结果应有助于更好地了解神经肌肉疾病中细胞丢失之前的早期突触缺陷。
