| Autor: |
David Finkelstein, Mohammad Haddadi, Samaneh Reiszadeh Jahromi, Saraf R. Ramesh |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.1101/2020.02.28.969501 |
| Popis: |
Parkinson’s disease (PD) is a class of neurodegenerative disorders in which, complex interactions of genetic and environmental agents are involved in the etiology of both sporadic and familial PD cases. α-synuclein-encodingSNCAgene is known as one of the major genetic contributors of this disease.E46Kmutation inSNCAgene has not been investigated as intensive as otherSNCAgene mutations including A30P and A53T. In this study, to induce PD inDrosophilaflies,UAS-hSNCAWTandUAS-hSNCAE46Ktransgenic fly lines were constructed, whereSNCAgene was over-expressed in flies brains using GAL4-UAS genetic system. Western blot analysis of head samples ofSNCA-expressing flies verifiedSNCAexpression at protein level. Light and electron microscopy analysis of ommatidial structures were performed to verify neurodegeneration as a result of α-synuclein gene overexpression inDrosophilatransgenic flies. Confocal microscopy analysis of dopaminergic neuron clusters verified cell loss followingSNCAE46Kexpression in the flies’ brain.E46Kα-synuclein gene over-expression resulted in an evident decline in longevity as well as climbing ability of the flies. Biochemical studies of transgenic flies showed a remarkable decline in antioxidant enzymes activity and a significant increase in oxidative markers level as well as AchE enzyme activity. Oxidative stress has been known as a causal factor in PD pathogenesis, following expression ofE46Kmutant version of humanSNCAgene. ThisDrosophilamodel is able to facilitate comparative studies of both molecular and cellular assays implicated in the assessment of neurotoxicity of different α-synuclein mutations. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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