Abstract: Parkinson’s disease(PD) is the second most common neurodegenerative disease in the world. Recent studies have demonstrated the presence of dysfunctional iron metabolism in patients with PD. This study constructed a Drosophila PD model by targeting mutations in the PINK1 gene in dopaminergic neuron(DA) using the Uas-Ga14 system. To investigate the role of the inhibitor of ferroptosis in PD, the study examined the motor ability, iron level in the brain, reactive oxygen species(ROS) level, lipid peroxidation level and number of DA in three groups of Drosophila: control( $ W^{118} $), PD model( $ PINK1^{B9} $) and Ferrostatin-1(Fer1) treatment( $ PINK1^{B9} $-Fer-1) groups. The results showed that the model group of Drosophila had decreased motor ability, increased iron content in the brain, increased ROS and lipid peroxidation levels, and decreased number of DA compared with the control group. Meanwhile, adding the ferroptosis inhibitor Fer-1 could effectively improve the motor phenotype, reduce the levels of ROS and lipid peroxidation and increase the number of DA. In summary, ferroptosis was present in the PD model constructed by mutating the PINK1 gene, and the symptoms could be rescued by Fer-1 treatment. This finding provides a new direction for the subsequent study of the pathological mechanism of PD.
Keywords: Parkinson’s disease(PD); ferroptosis; iron; reactive oxygen species(ROS); lipid peroxidation; dopaminergic neuron(DA)
合肥工业大学学报自科版