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

被引：33
作者：
Cao, Pengxiu [1 ]
Yuan, Yiyuan [1 ]
Pehek, Elizabeth A. [2 ,3 ,4 ]
Moise, Alex R. [1 ]
Huang, Ying [1 ]
Palczewski, Krzysztof [1 ]
Feng, Zhaoyang [1 ,5 ]
机构：
[1] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA
[4] Louis Stokes Cleveland Vet Affairs Med Ctr, Dept Vet Affairs, Cleveland, OH USA
[5] Xi An Jiao Tong Univ, Coll Med, Dept Physiol, Xian 710049, Shaanxi, Peoples R China
来源：
PLOS ONE | 2010年 / 5卷 / 02期
关键词：
PARKINSONS-DISEASE; C-ELEGANS; DROSOPHILA MODEL; NEURITE OUTGROWTH; GENE; NEUROTOXICITY; PATHOGENESIS; MECHANISMS; STORAGE; PHOSPHORYLATION;
D O I：
10.1371/journal.pone.0009312
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：8
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