Exploring the Interaction of Drosophila TDP-43 and the Type II Voltage-Gated Calcium Channel, Cacophony, in Regulating Motor Function and Behavior.
Exploring the Interaction of Drosophila TDP-43 and the Type II Voltage-Gated Calcium Channel, Cacophony, in Regulating Motor Function and Behavior.
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DOI：
10.1177/1179069517740892
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发表时间：
2017
影响因子：
--
通讯作者：
Morton DB
中科院分区：
文献类型：
--
作者：
Lembke KM;Morton DB
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是最常见的成人运动神经退行性疾病。这种疾病的原因仍然不清楚，因此没有有效的治疗或治愈方法。肌萎缩侧索硬化症和其他神经退行性疾病的特征通常是RNA结合蛋白TDP-43功能障碍。使用模型系统来理解TDP-43功能障碍的机制应该加速治疗靶点的识别。最近的一份报告表明，由果蝇TDP-43直系同源物tbph缺失引起的运动缺陷不是由神经肌肉接头处的生理变化引起的。相反，tbph突变体表现出的有缺陷的运动爆发节律和协调性可以通过基因恢复运动神经元或大脑中一对神经元的电压门控钙通道来挽救。如果这些作用反映在人类TDP-43蛋白病中，这些观察结果可能为研究这些神经退行性疾病的替代治疗靶点开辟新途径。
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neurodegenerative disease. The cause of the disease remains obscure, and as such there is no effective treatment or cure. Amyotrophic lateral sclerosis and other neurodegenerative diseases are frequently characterized by dysfunction of the RNA-binding protein, TDP-43. Using model systems to understand the mechanisms underlying TDP-43 dysfunction should accelerate identification of therapeutic targets. A recent report has shown that motor defects caused by the deletion of the Drosophila TDP-43 ortholog, tbph, are not driven by changes in the physiology at the neuromuscular junction. Rather, defective motor burst rhythmicity and coordination, displayed by tbph mutants, are rescued by genetically restoring a voltage-gated calcium channel to either motor neurons or just a single pair of neurons in the brain. If these effects are mirrored in human TDP-43 proteinopathies, these observations could open new avenues to investigate alternative therapeutic targets for these neurodegenerative diseases.