Transgenic drosophila model to study apolipoprotein E4-induced neurodegeneration

Haddadi, Mohammad and Nongthomba, Upendra and Jahromi, S. R. and Ramesh, S. R. (2016) Transgenic drosophila model to study apolipoprotein E4-induced neurodegeneration. Behavioural Brain Research, 301. 10 - 18.

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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.

Item Type: Article
Uncontrolled Keywords: Human apolipoprotein E, Neurodegeneration, Transgenic model
Subjects: B Life Science > Zoology
Divisions: Department of > Zoology
Depositing User: Manjula P Library Assistant
Date Deposited: 21 Jun 2019 11:33
Last Modified: 18 Sep 2019 11:26

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