PT  - JOURNAL ARTICLE
AU  - Tzu-Kang Sang
AU  - Hui-Yun Chang
AU  - George M. Lawless
AU  - Anuradha Ratnaparkhi
AU  - Lisa Mee
AU  - Larry C. Ackerson
AU  - Nigel T. Maidment
AU  - David E. Krantz
AU  - George R. Jackson
TI  - A <em>Drosophila</em> Model of Mutant Human Parkin-Induced Toxicity Demonstrates Selective Loss of Dopaminergic Neurons and Dependence on Cellular Dopamine
AID  - 10.1523/JNEUROSCI.4810-06.2007
DP  - 2007 Jan 31
TA  - The Journal of Neuroscience
PG  - 981--992
VI  - 27
IP  - 5
4099  - http://www.jneurosci.org/content/27/5/981.short
4100  - http://www.jneurosci.org/content/27/5/981.full
SO  - J. Neurosci.2007 Jan 31; 27
AB  - Mutations in human parkin have been identified in familial Parkinson's disease and in some sporadic cases. Here, we report that expression of mutant but not wild-type human parkin in Drosophila causes age-dependent, selective degeneration of dopaminergic (DA) neurons accompanied by a progressive motor impairment. Overexpression or knockdown of the Drosophila vesicular monoamine transporter, which regulates cytosolic DA homeostasis, partially rescues or exacerbates, respectively, the degenerative phenotypes caused by mutant human parkin. These results support a model in which the vulnerability of DA neurons to parkin-induced neurotoxicity results from the interaction of mutant parkin with cytoplasmic dopamine.