Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration

Haddadi, Mohammad and Nongthomba, Upendra and Jahromi, Samaneh Reiszadeh and Ramesh, SR (2016) Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration. In: BEHAVIOURAL BRAIN RESEARCH, 301 . pp. 10-18.

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Abstract

The epsilon 4 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 epsilon 3 and epsilon 4 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. (C) 2015 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Publication:	BEHAVIOURAL BRAIN RESEARCH
Publisher:	ELSEVIER SCIENCE BV
Additional Information:	Copy right for this article belongs to the ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Keywords:	Human apolipoprotein E; Neurodegeneration; Transgenic Drosophila model
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	01 Apr 2016 05:06
Last Modified:	01 Apr 2016 05:06
URI:	http://eprints.iisc.ac.in/id/eprint/53448

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