Mutant alpha-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson's disease.
Parkinson's disease (PD) patients show a characteristic loss of motor control caused by the degeneration of dopaminergic neurons. Mutations in the genes that encode alpha-synuclein and parkin have been linked to inherited forms of this disease. The parkin protein functions as a ubiquitin ligase that targets proteins for degradation. Expression of isoforms of human alpha-synuclein in the Drosophila melanogaster nervous system forms the basis of an excellent genetic model that recapitulates phenotypic and behavioural features of PD. Using this model, we analysed the effect of parkin co-expression on the climbing ability of aging flies, their life span, and their retinal degeneration. We have determined that co-expression of parkin can suppress phenotypes caused by expression of mutant alpha-synuclein. In the developing eye, parkin reduces retinal degeneration. When co-expressed in the dopaminergic neurons, the ability to climb is extended over time. If conserved in humans, we suggest that upregulation of parkin may prove a method of suppression for PD induced by mutant forms of alpha-synuclein.
Haywood
Annika F M
AF
Department of Biology, Memorical University of Newfoundland, St. John's, Canada.
Staveley
Brian E
BE
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D009043:Motor Activity / Q000235:genetics; D050505:Mutant Proteins; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein / Q000235:genetics* / Q000502:physiology*
D029721:Drosophila Proteins; D050505:Mutant Proteins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C487430:park protein, Drosophila; D004298:Dopamine