A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine.

TitleA Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine.
Publication TypeJournal Article
Year of Publication2007
AuthorsSang, T-K, Chang H-Y, Lawless GM, Ratnaparkhi A, Mee L, Ackerson LC, Maidment NT, Krantz DE, Jackson GR
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume27
Issue5
Pagination981-92
Date Published2007 Jan 31
ISSN1529-2401
KeywordsAge Factors, Animals, Animals, Genetically Modified, Brain, Cell Count, Disease Models, Animal, Dopamine, Drosophila, Drosophila Proteins, Gene Expression Regulation, Humans, Mutation, Nerve Degeneration, Neurons, Ubiquitin-Protein Ligases
Abstract

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.

Alternate JournalJ. Neurosci.