title: Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration.
abstract: The ε4 isoform of apolipoprotein E (ApoE4) that is involved in neuron-glial lipid metabolism has been demonstrated as the main genetic risk factor in late-onset of Alzheimer's disease. However, the mechanism underlying ApoE4-mediated neurodegeneration remains unclear. We created a transgenic model of neurodegenerative disorder by expressing ε3 and ε4 isoforms of human ApoE in the Drosophila melanogaster. The genetic models exhibited progressive neurodegeneration, shortened lifespan and memory impairment. Genetic interaction studies between amyloid precursor protein and ApoE in axon pathology of the disease revealed that over expression of hApoE in Appl-expressing neurons of Drosophila brain causes neurodegeneration. Moreover, acute oxidative damage in the hApoE transgenic flies triggered a neuroprotective response of hApoE3 while chronic induction of oxidative damage accelerated the rate of neurodegeneration. This Drosophila model may facilitate analysis of the molecular and cellular events implicated in hApoE4 neurotoxicity.
authors.affiliation: Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haddadi
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
authors.forename: Upendra
authors.initials: U
authors.lastname: Nongthomba
authors.affiliation: Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
authors.forename: Samaneh Reiszadeh
authors.initials: SR
authors.lastname: Jahromi
authors.affiliation: Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore, Karnataka, India. Electronic address: rameshuom@gmail.com.
authors.forename: S R
authors.initials: SR
authors.lastname: Ramesh
mesh_terms: D000375:Aging / Q000378:metabolism / Q000523:psychology; D000818:Animals; D030801:Animals, Genetically Modified; D053318:Apolipoprotein E3 / Q000235:genetics* / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000378:metabolism*; D054910:Compound Eye, Arthropod / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D008568:Memory / Q000502:physiology; D024521:Mushroom Bodies / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D055696:Olfactory Perception / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D017382:Reactive Oxygen Species
keywords: Human apolipoprotein E; Neurodegeneration; Transgenic Drosophila model