Research About The Expression Of Trim27in Parkinson’s Disease And The Role Of It In The Neuronal Apoptosis

Objective:Apoptosis is one of the major causes of Parkinson’s disease. Our goal is toinvestigate the role of Trim27in the pathogenesis of Parkinson’s disease, in order toprovide novel theraputic targets for treatment of Parkinson’s disease.Methods:Western blot and qPCR were used to determine the expression of Trim27in thePBMC between patients of Parkinson’s and healthy individuals and in the PC12cellstreated with1-methyl-4-phenylpyridinium（MPP+）and in the SNpc of the PD mousemodel. Trim27siRNA knockdown, together with Trim27-/-mice, was used to studythe effects of Trim27silence in PC12cell apoptosis and dopaminergic neuron loss,respectively.Results:Compared to healthy individuals, Trim27mRNA was obviously upregulated inpatients with PD. Exposure of PC12cells to50μM MPP+for24h induced asignificant increased number of apoptotic cells.The expression of cleaved Caspase-3was highly upregulated after MPP+treatment, while the level of TH expression wasdramatically reduced. The expression of Trim27was also significantly enhanced.Knock down of Trim27mediated by Trim27siRNAs decreased its expressionmarkedly and diminished the Cleaved Caspase-3level induced by MPP+treatment.Mechanically, Trim27promoted apoptosis through activating NF-κB signaling. Therewere much fewer TH-positive neurons in the SNpc of MPTP-treated mice. Theexpression of active caspase-3and Trim27was markedly increased while the expression of TH was reduced in the SNpc of MPTP-treated mice using Western blotanalysis. There are reduced dopaminergic neuron loss and lower apoptotic proteincaspase-3expression levels in MPTP-treated Trim27-/-mice, compared withMPTP-treated WT mice.Conclusion:Trim27was significantly upregulated in patients with PD. We further showedthat Trim27expression was dramatically induced in PC12cells and in the SNpc of thePD mouse model. RNAi-mediated knockdown of Trim27in PC12cells showedobvious suppression of apoptosis. Mechanically, Trim27promoted apoptosis throughactivating NF-κB signaling. There are reduced dopaminergic neuron loss and lowerapoptotic protein expression levels in MPTP-treated Trim27-/-mice, compared withMPTP-treated WT mice. These data demonstrated that Trim27deficiency decreasesapoptosis and protects dopaminergic neurons in the neurotoxin model of PD.