Research On Neuroprotective Role Of Parkin In AD Transgenic Drosophila Models And Its Effect Mechanism Of Parkin

Objective:Alzheimer’s disease(AD),a common neurodegenerative disease, is characterized clinically by a progressive loss of cognition impairment and memory function.The characteristics of pathological changes including: ① β-amyloid deposition ②The hyperphosphorylation of Tau protein lead to neurofibrillary tangles(NFT).The excessive phosphorylated of Tau protein, However, has become a hot topic about the AD in recent years. Parkin,a particular protein, encoding by PARK2, is an ubiquitin protein ligase of E3.Parkin mediate Ubiquitination of substrate proteins,so that toxic protein, mediating Ubiquitination by Parkin, was degraded; what’s more, Parkin, mediating mitochondrial fission, contributes to the clearance of impaired mitochondria by mitochondrial autophagy pathway to improve mitochondrial function. In this experiment,we, using a AD transgenic Drosophila model, investigate whether upregulated expression of Parkin can play a neuroprotective role in AD and how it works. Methods:Here,using the classical model of GAL4/UAS system,and ninaE- GAL4/UAS system AD transgenic Drosophila models were constructed by using the promoter ninaE-GAL4,which drive hTauR406 W protein( Tau protein which mutation site is at R406W),selectively expression in cells of Drosophila eyes.Then,Parkin protein was expressed in AD transgenic Drosophila models by genetic methods with or without in a background of mitochondrial fission protein of Drp1.Then we detect the mRNA level of Drp1 and Parkin,using the real time-PCR.The change of drosophila compound eyes were also observed by us, using the light microscope and electron microscope.we also detect the ATP level of the head of drosophila. Results:AD transgenic drosophila model of the ninaE-GAL4/UAS system was constructed by us successfully, and then we expressed upregulation of Parkin in this model successfully. We found that the significant retinal structure was destroyed,ATP content of the brain of AD transgenic drosophila model of the ninaE-GAL4/UAS system was decreased. However, after upregulating the expression of Parkin in this model, the significant retinal structure was restored, the ATP content of the brain was improved. however,with the ATP content of the brain decreased,the significant retinal structure was destroyed again in a background of knockdown of mitochondrial fission protein of Drp1.Con clusion:It is confirmed that expression of Parkin could protect AD transgenic Drosophila models,and the protection role of Parkin is Drp1- dependent,maybe.