Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan; Kansai Gakken Laboratory, Kankyo Eisei Yakuhin Co. Ltd., Seika-cho, Kyoto, 619-0237, Japan.
Department of Biological Sciences, Konkuk University, Seoul, Republic of Korea.
Exp Cell Res. 2021 Jun 1;403(1):112584. doi: 10.1016/j.yexcr.2021.112584. Epub 2021 Apr 1.
Drosophila is emerging as a convenient model for investigating human diseases. Functional homologues of almost 75% of human disease-related genes are found in Drosophila. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes defects in motoneurons. Charcot-Marie-Tooth disease (CMT) is one of the most commonly found inherited neuropathies affecting both motor and sensory neurons. No effective therapy has been established for either of these diseases. In this review, after overviewing ALS, Drosophila models targeting several ALS-causing genes, including TDP-43, FUS and Ubiquilin2, are described with their genetic interactants. Then, after overviewing CMT, examples of Drosophila models targeting several CMT-causing genes, including mitochondria-related genes and FIG 4, are also described with their genetic interactants. In addition, we introduce Sotos syndrome caused by mutations in the epigenetic regulator gene NSD1. Lastly, several genes and pathways that commonly interact with ALS- and/or CMT-causing genes are described. In the case of ALS and CMT that have many causative genes, it may be not practical to perform gene therapy for each of the many disease-causing genes. The possible uses of the common genes and pathways as novel diagnosis markers and effective therapeutic targets are discussed.
果蝇正成为研究人类疾病的一种便利模式。在果蝇中发现了近 75%的人类疾病相关基因的功能同源物。肌萎缩侧索硬化症（ALS）是一种严重的神经退行性疾病，导致运动神经元缺陷。Charcot-Marie-Tooth 病（CMT）是最常见的遗传性神经病之一，影响运动和感觉神经元。对于这两种疾病都没有有效的治疗方法。在这篇综述中，在概述 ALS 之后，描述了针对包括 TDP-43、FUS 和 Ubiquilin2 在内的几个导致 ALS 的基因的果蝇模型，以及它们的遗传相互作用物。然后，在概述 CMT 之后，还描述了针对几个导致 CMT 的基因的果蝇模型，包括与线粒体相关的基因和 FIG4，以及它们的遗传相互作用物。此外，我们介绍了由表观遗传调节剂基因 NSD1 突变引起的 Sotos 综合征。最后，描述了与 ALS 和/或 CMT 致病基因共同作用的几个基因和途径。在 ALS 和 CMT 有许多致病基因的情况下，对许多致病基因进行基因治疗可能不切实际。讨论了将常见基因和途径用作新型诊断标志物和有效治疗靶点的可能性。
