Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Adv Exp Med Biol. 2018;1076:79-95. doi: 10.1007/978-981-13-0529-0_6.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects upper and lower motor neurons in the brain and the spinal cord. Due to the progressive neurodegeneration, ALS leads to paralysis and death caused by respiratory failure 2-5 years after the onset of symptoms. There is no effective cure available. Most ALS cases are sporadic, without family history, whereas 10% of the cases are familial. Identification of variants in more than 30 different loci has provided insight into the pathogenic molecular mechanisms mediating disease pathogenesis. Studies of a Drosophila melanogaster model for each of the ALS genes can contribute to uncovering pathophysiological mechanism of ALS and finding targets of the disease-modifying therapy. In this review, we focus on three ALS-causing genes: TAR DNA-binding protein (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and chromosome 9 open reading frame 72 (C9orf72).
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，影响大脑和脊髓中的上下运动神经元。由于进行性神经退行性变，ALS 导致症状出现后 2-5 年内因呼吸衰竭而瘫痪和死亡。目前尚无有效的治疗方法。大多数 ALS 病例为散发性，无家族史，而 10%的病例为家族性。在 30 多个不同基因座的变异体的鉴定为介导疾病发病机制的致病分子机制提供了深入了解。对每个 ALS 基因的黑腹果蝇模型的研究有助于揭示 ALS 的病理生理机制并找到疾病修饰治疗的靶点。在这篇综述中，我们重点介绍了三个导致 ALS 的基因：TAR DNA 结合蛋白（TDP-43）、肉瘤融合/脂肪肉瘤易位（FUS/TLS）和染色体 9 开放阅读框 72（C9orf72）。
