title: Neurophysiology of Drosophila models of Parkinson's disease.
abstract: We provide an insight into the role Drosophila has played in elucidating neurophysiological perturbations associated with Parkinson's disease- (PD-) related genes. Synaptic signalling deficits are observed in motor, central, and sensory systems. Given the neurological impact of disease causing mutations within these same genes in humans the phenotypes observed in fly are of significant interest. As such we observe four unique opportunities provided by fly nervous system models of Parkinson's disease. Firstly, Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. Secondly, models show noncell autonomous signalling within the nervous system, offering the opportunity to develop our understanding of the way pathogenic signalling propagates, resembling Braak's scheme of spreading pathology in PD. Thirdly, the models link physiological deficits to changes in synaptic structure. While the structure-function relationship is complex, the genetic tractability of Drosophila offers the chance to separate fundamental changes from downstream consequences. Finally, the strong neuronal phenotypes permit relevant first in vivo drug testing.
authors.affiliation: Department of Biology, University of York, York YO1 5DD, UK.
authors.forename: Ryan J H
authors.initials: RJ
authors.lastname: West
authors.affiliation: Department of Biology, University of York, York YO1 5DD, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Furmston
authors.affiliation: Department of Biology, University of York, York YO1 5DD, UK ; The MRC Protein Phosphorylation and Ubiquitylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Charles A C
authors.initials: CA
authors.lastname: Williams
authors.affiliation: Department of Biology, University of York, York YO1 5DD, UK.
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Elliott