Alpha-Synuclein Disrupted Dopamine Homeostasis Leads to Dopaminergic Neuron Degeneration in Caenorhabditis elegans

作者：Cao Pengxiu^*; Yuan Yiyuan; Pehek Elizabeth A; Moise Alex R; Huang Ying; Palczewski Krzysztof; Feng Zhaoyang

来源：PLos One, 2010, 5(2): e9312.

DOI：10.1371/journal.pone.0009312

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.

• 出版日期2010-2-19
• 单位西安交通大学