The FBXO7 homologue nutcracker and binding partner PI31 in Drosophila melanogaster models of Parkinson Disease

Parkinson Pyramidal Syndrome is an early onset form of Parkinson Disease (PD) that has additional degenerative effects in the extrapyramidal region of the brain resulting in a more severe and faster developing form of disease. Improper turnover of cellular components and a build-up of toxic protein aggregates have been implicated as causative factors in the onset of this disease. Protein removal is mediate by an intracellular proteasome complex. The targeting component of this complex, an E3 ubiquitin ligase, is essential for proper function. FBXO7 is the F-box component of a form of the SCF E3 ubiquitin ligase that has been found to be linked to familial forms of Parkinson Pyramidal Syndrome. The putative Drosophila melanogaster homologue of this gene, nutcracker, and a binding partner, PI31, have been shown to be active in proteasome function. We show that altered expression of either ntc or PI31 in dopaminergic neurons leads to a decrease in longevity and locomotor ability, phenotypes both associated with models of PD. Furthermore, expression of ntc-RNAi in an established, Îą-synuclein-dependent, model of PD may be sufficient to rescue phenotypes of diminished longevity and locomotor control. Further characterization of these pathways may lead to new therapeutic approaches to combat PD.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author