Research PINK1 On SCA3 / MJD Transgenic Drosophila Model Of Neuroprotective Mechanism Of Action

Objective: The hereditary spinocerebellar ataxias (SCAs) are agenetically heterogeneous group of neurodegenerative disorderscharacterized by ataxia, tremble, poor coordination of hands,speech,and eye movements，pyramid and extra pyramid sign, most of them areinherited in an autosomal dominant manner. Spinocerebellar ataxia type3, also known as Machado Joseph disease (SCA3/MJD), is the mostcommon genotype of SCAs in world. In SCA3/MJD gene MJD1codingCAG three nucleic acid sequence repeats more than the normal, thelonger the repeat, the earlier the onset and the more severe the disease.PINK1is the one of the most important gene in Parkinson Disease (PD).Although SCA3/MJD and PD with different clinical character, but theybelong to the neurodegenerative disease, the patients of SCA3/MJD mayalso appear the symptoms of Parkinson’s disease. It has been shown, themutation of PINK1and other mitochondrial proteins related to disorder ofmitochondrial function the caused the PD. Drosophila is a small animal, itis easy to operate playing an important role in research ofneurodegenerative and neurogenetic disorders. To date, many transgenicdrosophila models were set up for neurodegenerative and neurogeneticdisorders including SCA3/MJD. This study is intended to explore therelationship between mitochondrial dysfunction and SCA3/MJD and the effect of PINK1gene on SCA3/MJD use transgenic drosophila models.Methods: We used the gene promoter Nrv2-GAL4and GAL4-UAStransformation system and expressed a truncated version of the humanataxin-3protein (MJDtr-Q78) in both the motor neurons, respectively.Then, PINK1protein was expressed in SCA3/MJD transgenic drosophilamodels by cross method. These groups of drosophila were tested flight,wing developmental defects, survival, ATP. Results: we constructed theSCA3/MJD transgenic drosophila models of Nrv2-GAL4/UAS systemand expressed the PINK1gene in drosophila models successfully. TheFlight ability was significantly weakened, Wing shaped rate wasincreased, survival rate was reduced, and ATP content was reduced in theSCA3/MJD transgenic drosophila models. Whether overexpression orRNA interfere of PINK1gene in the SCA3/MJD transgenic drosophilamodels, significant improved flight ability, wing developmental defects,survival, and the content of ATP. Conclusions: Mitochondrialdysfunction plays an important role in the pathogenesis of SCA3/MJD.PINK1gene expression and RNAinterfere has neuroprotective effect onNrv2-GAL4system of SCA3/MJD transgenic drosophila models. Thisprotection affected SCA3/MJD transgenic drosophila models byregulation of mitochondrial fission and fusion and promoting the role ofmitochondrial function.