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

## TL;DR

This study shows that Serping1 siRNA treatment helps protect brain cells in a mouse model of Parkinson’s disease by reducing inflammation and harmful protein buildup.

## Contribution

The study introduces Serping1 siRNA as a novel therapeutic approach for Parkinson’s disease by targeting inflammation and α-synuclein phosphorylation.

## Key findings

- Serping1 siRNA improved motor ability and tyrosine hydroxylase levels in the substantia nigra and striatum.
- Serping1 siRNA reduced pSer129-α-syn levels more effectively than N-acetylcysteine.
- Serping1 siRNA decreased inflammation markers cyclooxygenase-2 and inducible nitric oxide synthase.

## Abstract

Background: 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). Serping1 is an important gene for controlling blood vessel maintenance; including the process of inflammation. Methods: Increased expression of Serping1 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 Serping1 siRNA treatment has a therapeutic effect in this model. Results: We demonstrated that this treatment shows a normal status in the motor ability test and TH level in the SN and striatum. Serping1 siRNA was found to react to decreased Serping1 levels in the SN. In the pSer129-α-syn level of the SN region; Serping1 siRNA had a greater positive effect on PD than N-acetylcysteine by inhibiting pSer129-α-syn formation. Cyclooxygenase-2 and inducible nitric oxide synthase levels were decreased by Serping1 siRNA treatment; thereby indicating its effect on inflammation. Conclusions: Our findings suggest that Serping1 siRNA may represent a potential therapeutic approach for PD; warranting further investigation.