The Role Of Mitochondrial Unfolded Protein Response In Sir2 Suppresses The Neurodegeneration Of PD Transgenic Drosophila

Objective: Parkinson’s disease(idiopathic Parkinson’s disease, PD), referred as PD, is the second most common neurodegenerative disease. In recent decades, the study shows that the lack of PINK1(PTEN-induced putative kinase 1) can lead to mitochondria dysfunction which is a significant cause of PD pathogenesis. Sir2(Silent information regulator 2) belongs to the family of sirtuin proteins. It has found that Sir2 can induce mitochondrial unfolded protein response(UPRmt) and improve mitochondrial function in recent studies. To data, many transgenic drosophila models were set up for neurodegenerative diseases including PD. This study is intended to explore whether Sir2 overexpression has the neuroprotective effect on PD transgenic drosophila models and the relevance with UPRmt.Methods: We used the gene Mhc-GAL4 promoter and the classical GAL4-UAS transformation system to construct PD transgenic Drosophila models-Pink1B9 which could be expressed in Drosophila muscles by genetic intervention, then with testing flying, wing development defects, the content of ATP and the levels of mRNA to invest whether Sir2 overexpression in PD transgenic Drosophila models of the Mhc-GAL4/UAS system has neuroprotective effects on neurodegeneration. By Inhibiting the chaperone Hsp60 and GCN-2 expression associated with UPRmt by RNA interference, we observed the role of Sir2 overexpression in suppressing neurodegeneration in PD transgenic Drosophila models and verified the correlation of UPRmt with testing the flying, wing development defects and the levels of chaperone mRNA.Results: We constructed the Pink1B9 PD transgenic Drosophila models, Sir2 overexpression in PD transgenic Drosophila models and inhibition of UPRmt with Sir2 overexpression in PD transgenic Drosophila models of the Mhc-GAL4/UAS system. Sir2 overexpression suppressed PD transgenic Drosophila models motor neuron degeneration, improved the flight ability, reduced the wing shaped rate, increased the content of ATP and significantly improved the athletic ability. The effect of Sir2 was weakened by inhibiting UPRmt.Conclusion: Sir2 overexpression has neuroprotective effects on PD transgenic Drosophila which is associated with UPRmt.