The Caenorhabditis elegans dopaminergic system:: Opportunities for insights into dopamine transport and neurodegeneration

被引:84
作者
Nass, R [1 ]
Blakely, RD
机构
[1] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Nashville, TN 37232 USA
关键词
nematode; genetics; Parkinson's disease; apoptosis; 6-OHDA;
D O I
10.1146/annurev.pharmtox.43.100901.135934
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The neurotransmitter dopamine (DA) plays a central role in the coordination of movement, attention, and the recognition of reward. Loss of DA from the basal ganglia, as a consequence of degeneration of neurons in the substantia nigra, triggers postural instability and Parkinson's disease (PD). DA transporters (DATs) regulate synaptic DA availability and provide a conduit for the uptake of DA mimetic neurotoxins, which can be used to evoke neuronal death and Parkinson-like syndrome. Recently, we have explored the sensitivity of DA neurons in the nematode Caenorhabditis elegans to the Parkinsonian-inducing neurotoxin 6-hydroxydopamine (6-OHDA) and found striking similarities, including DAT dependence, to neurodegeneration observed in mammalian models. In this review, we present our findings in the context of molecular and behavioral dimensions of DA signaling in C. elegans with an eye toward opportunities for uncovering DAT mutants, DAT regulators, and components of toxin-mediated cell death.
引用
收藏
页码:521 / 544
页数:28
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