Effect of Serping1 siRNA Injection on Dopaminergic Cell Reduction in an MPTP-Induced Parkinson’s Disease Mouse Model

<b>Background</b>: Decreased dopaminergic cells and tyrosine hydroxylase (TH) in the substantia nigra (SN) lead to Parkinson's disease (PD); but its cause remains unknown. PD is characterized by α-synuclein (α-syn) accumulation in Lewy bodies; most of which is phosphorylated at Ser129 (pSer129 α-syn). <i>Serping1</i> is an important gene for controlling blood vessel maintenance; including the process of inflammation. <b>Methods</b>: Increased expression of <i>Serping1</i> affects dopaminergic cell death in the SN of a chronic PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); and <i>Serping1</i> siRNA treatment has a therapeutic effect in this model. <b>Results</b>: We demonstrated that this treatment shows a normal status in the motor ability test and TH level in the SN and striatum. <i>Serping1</i> siRNA was found to react to decreased <i>Serping1</i> levels in the SN. In the pSer129-α-syn level of the SN region; <i>Serping1</i> siRNA had a greater positive effect on PD than <i>N</i>-acetylcysteine by inhibiting pSer129-α-syn formation. Cyclooxygenase-2 and inducible nitric oxide synthase levels were decreased by <i>Serping1</i> siRNA treatment; thereby indicating its effect on inflammation. <b>Conclusions</b>: Our findings suggest that <i>Serping1</i> siRNA may represent a potential therapeutic approach for PD; warranting further investigation.