Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration
| Autor: | Samaneh Reiszadeh Jahromi, Upendra Nongthomba, Saraf R. Ramesh, Mohammad Haddadi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Aging Transgene Apolipoprotein E4 Apolipoprotein E3 Neuroprotection Transgenic Model Animals Genetically Modified 03 medical and health sciences Behavioral Neuroscience Memory Genetic model medicine Amyloid precursor protein Animals Humans Compound Eye Arthropod Mushroom Bodies Neurons biology Neurodegeneration Retinal Degeneration Neurotoxicity Neurodegenerative Diseases medicine.disease Olfactory Perception Disease Models Animal Oxidative Stress 030104 developmental biology Drosophila melanogaster biology.protein lipids (amino acids peptides and proteins) Reactive Oxygen Species Neuroscience |
| Zdroj: | Behavioural brain research. 301 |
| ISSN: | 1872-7549 |
| Popis: | The e4 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 e3 and e4 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. |
| Databáze: | OpenAIRE |
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