Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila
Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila
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DOI：
10.1016/j.neurobiolaging.2006.09.004
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Kim, Jaeseob
中科院分区：
文献类型：
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作者：
Lee, Youngseok;Paik, Donggi;Kim, Jaeseob
遗传性痉挛性截瘫 (HSP) 是一种人类遗传性疾病，会导致下肢僵硬增加和肌肉反射过度活跃。 atlastin (ad) 是导致 HSP 突变的主要基因之一。我们生成了 HSP 的果蝇模型，该模型在 atl 中具有无效突变。随着年龄的增长，atl null果蝇会因碰撞或涡旋等机械冲击而瘫痪。此外，果蝇表现出多巴胺能神经元的年龄依赖性退化。通过在多巴胺能神经元中靶向表达 atl 或喂食 L-DOPA 或 SK&F 38393（一种多巴胺受体激动剂），可以挽救这些表型。我们的数据提出了一种可能性，即携带所有突变的人类患者的 HSP 疾病症状的原因之一是多巴胺能神经元的功能障碍或退化。 (C) 2006 Elsevier Inc. 保留所有权利。
Hereditary spastic paraplegias (HSPs) are human genetic disorders causing increased stiffness and overactive muscle reflexes in the lower extremities. atlastin (ad) is one of the major genes in which mutations result in HSP. We generated a Drosophila model of HSP that has a null mutation in atl. As they aged, atl null flies were paralyzed by mechanical shock such as bumping or vortexing. Furthermore, the flies showed age-dependent degeneration of dopaminergic neurons. These phenotypes were rescued by targeted expression of atl in dopaminergic neurons or feeding L-DOPA or SK&F 38393, an agonist of dopamine receptor. Our data raised the possibility that one of the causes of HSP disease symptoms in human patients with all mutations is malfunction or degeneration of dopaminergic neurons. (C) 2006 Elsevier Inc. All rights reserved.