Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
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DOI：
10.1073/pnas.042497999
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发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Blakely, RD
中科院分区：
文献类型：
--
作者：
Nass, R;Hall, DH;Blakely, RD
帕金森病是一种复杂的神经退行性疾病，其特征是大脑多巴胺神经元的死亡。在哺乳动物中，多巴胺神经元变性可通过暴露于突触前多巴胺转运蛋白 (DAT) 积累的神经毒素而引发，包括 6-羟基多巴胺 (6-OHDA) 和 1-甲基-4-苯基吡啶鎓。我们建立了一个系统，用于对秀丽隐杆线虫中神经毒素诱导的多巴胺神经元死亡进行药理学和遗传学评估。将绿色荧光蛋白标记的活蠕虫短暂（11 小时）暴露于 6-OHDA 会导致多巴胺神经元选择性变性。我们证明干扰 DAT 功能的药物可以防止 6-OHDA 毒性。 6-OHDA 触发的神经变性不需要 CED-3/CED-4 细胞死亡途径，但会通过线虫 DAT 的遗传破坏而消除。
Parkinson's disease is a complex neurodegenerative disorder characterized by the death of brain dopamine neurons. In mammals, dopamine neuronal degeneration can be triggered through exposure to neurotoxins accumulated by the presynaptic dopamine transporter (DAT), including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium. We have established a system for the pharmacological and genetic evaluation of neurotoxin-induced dopamine neuronal death in Caenorhabditis elegans. Brief (11 h) exposure of green fluorescent protein-tagged, living worms to 6-OHDA causes selective degeneration of dopamine neurons. We demonstrate that agents that interfere with DAT function protect against 6-OHDA toxicity. 6-OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT.