Response of A30P and A53T α-synuclein transgenic flies to antioxidant therapy: implication for Parkinson’s disease

Parkinson’s disease (PD) is characterized anatomically by degeneration of dopaminergic neurons, presence of Lewy bodies contain aggregated form of α-synuclein. Oxidative stress has been involved in neurodegeneration of PD cases. Genetic and environmental factors have been implicated in PD. Pesticides such as paraquat (PQ) and rotenone are involved in sporadicPD. Although, majority of PD cases are sporadic, several genes cause familial forms of PD, one of them is SNCA gene thatoverexpression of human wild type or mutant forms ( A30P, A53T and E46K) of it in Drosophila represents pathologicaland behavioral features of PD. Natural antioxidants have potential to delay the onset of PD. Therefore, we have investigated the neuroprotective effects of Dh root extract as a cocktail of antioxidant molecules in Drosophila PD model. To get PDmodel flies, first, we cloned CDNA of human α-synuclein gene into the GAL4-responsive PUAST expression vector by site-directed mutagenesis method. Then, we did microinjection to W118 embryo. To express SCNA gene, we crossed these flies with flies contain a pan-neural activating system (elav-Gal4 driver). Finally, we got transgenic flies that have shownbehavioral and pathological features of PD such as deterioration in circadian rhythm of locomotion, sensitivity toneurotoxins and neurodegeneration.We fed them by Dh extract for 25 days and neuruprotective action of Dh against PD symptoms and sensitivity to PQ have been investigated. Our results showed better performance of transgenic flies pre-fed by Dh extract in locomotion, PQ toxicicty assay and diminished level of ROS and LPO levels.

Keywords:

oxidative stress , transgenic line , Parkinson , Drosophila , neuroprotective effect