Alpha-Synuclein Disrupted Dopamine Homeostasis Leads to Dopaminergic Neuron Degeneration in Caenorhabditis elegans
Alpha-Synuclein Disrupted Dopamine Homeostasis Leads to Dopaminergic Neuron Degeneration in Caenorhabditis elegans
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DOI：
10.1371/journal.pone.0009312
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发表时间：
2010-02-19
期刊：
影响因子：
3.7
通讯作者：
Feng, Zhaoyang
中科院分区：
文献类型：
--
作者：
Cao, Pengxiu;Yuan, Yiyuan;Feng, Zhaoyang
多巴胺稳态的破坏可能导致多巴胺能神经元变性，这是帕金森病中多巴胺能神经元特异性脆弱性的一种解释。人α-突触核蛋白在C. elegans引起多巴胺能神经元变性，α-突触核蛋白对多巴胺稳态的影响及其在C.没有报道过秀丽线虫。在这里，我们研究了α-突触核蛋白过表达对蠕虫多巴胺稳态的影响。我们发现，α-突触核蛋白的表达导致多巴胺的合成和含量的上调，以及多巴胺能突触囊泡的重新分布，这显著有助于多巴胺能神经元变性。这些结果提供了体内证据，支持多巴胺稳态在支持多巴胺能神经元完整性中的关键作用。
Disruption of dopamine homeostasis may lead to dopaminergic neuron degeneration, a proposed explanation for the specific vulnerability of dopaminergic neurons in Parkinson's disease. While expression of human alpha-synuclein in C. elegans results in dopaminergic neuron degeneration, the effects of alpha-synuclein on dopamine homeostasis and its contribution to dopaminergic neuron degeneration in C. elegans have not been reported. Here, we examined the effects of alpha-synuclein overexpression on worm dopamine homeostasis. We found that alpha-synuclein expression results in upregulation of dopamine synthesis and content, and redistribution of dopaminergic synaptic vesicles, which significantly contribute to dopaminergic neuron degeneration. These results provide in vivo evidence supporting a critical role for dopamine homeostasis in supporting dopaminergic neuron integrity.