title: A comparison of the neuronal dysfunction caused by Drosophila tau and human tau in a Drosophila model of tauopathies.
abstract: Hyperphosphorylation and aggregation of tau into tangles is a feature of disorders such as Alzheimer's disease and other Tauopathies. To model these disorders in Drosophila melanogaster, human tau has been over-expressed and a variety of phenotypes have been observed including neurotoxicity, disrupted neuronal and synaptic function and locomotor impairments. Neuronal dysfunction has been seen prior to neuronal death and in the absence of tangle formation. The Drosophila tau protein shares a large degree of homology with human tau but differs in the crucial microtubule binding domains. Although like human tau Drosophila tau can induce neurotoxicity, little is known about its ability to disrupt neuronal function. In this study we demonstrate that like human tau, over-expression of Drosophila tau results in disrupted axonal transport, altered neuromuscular junction morphology and locomotor impairments. This indicates that like human tau, over-expression of Drosophila tau compromises neuronal function despite significant differences in microtubule binding regions.
authors.affiliation: Department of Neuroscience, University of Southampton, School of Biological Sciences, Bassett Crescent East, Southampton, SO16 7PX, UK.
authors.forename: Kiren K
authors.initials: KK
authors.lastname: Ubhi
authors.forename: Hassan
authors.initials: H
authors.lastname: Shaibah
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Newman
authors.forename: David
authors.initials: D
authors.lastname: Shepherd
authors.forename: Amritpal
authors.initials: A
authors.lastname: Mudher
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001370:Axonal Transport / Q000502:physiology; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007814:Larva; D009068:Movement / Q000502:physiology; D009469:Neuromuscular Junction / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D016875:tau Proteins