# Modulation of lncRNAs and oxidative stress related genes by N-acetylcysteine and S-methylcysteine in rotenone-induced Parkinson's disease

## TL;DR

This study shows that N-acetylcysteine and S-methylcysteine protect against Parkinson's disease by reducing oxidative stress and regulating lncRNA expression.

## Contribution

The novel contribution is the identification of N-acetylcysteine and S-methylcysteine's effects on lncRNAs and the Nrf2/Ho-1 pathway in a Parkinson's model.

## Key findings

- N-acetylcysteine and S-methylcysteine restored antioxidant gene expression and reduced oxidative stress in Parkinson's mice.
- Treatment reduced elevated lncRNA levels and improved antioxidant enzyme activity in brain and serum.
- Molecular docking and gene networks showed Nrf2 as a central regulator modulated by these compounds.

## Abstract

Oxidative stress and changes in lncRNA expression are key factors in the pathophysiology of Parkinson's disease. This study investigated the protective effects of N-acetylcysteine and S-methylcysteine on the expression of long non-coding RNAs and oxidative stress-related genes in the brain, as well as the activity of antioxidant enzymes in the brain and serum of mice with rotenone-induced Parkinson's disease. In this experimental study, 56 male BALB/c mice were utilized and treated continuously for 10 days. Gene expression of superoxide dismutase, glutathione peroxidase, catalase, Nrf2, Ho-1, and long non-coding RNAs Malat1, Neat1, and Gas5 in the brain was analyzed using real-time PCR. Biochemical assays measured antioxidant enzyme activities, malondialdehyde levels, and total antioxidant capacity in brain tissue and serum. A bioinformatics approach, including molecular docking and the construction of a gene interaction network, was also performed. Our data showed decreased expression of antioxidant genes and Nrf2 and Ho-1 regulatory factors in the Parkinson's group, which were significantly restored by N-acetylcysteine and S-methylcysteine treatments. Long non-coding RNAs were elevated in the Parkinson's disease model and reduced by interventions. Antioxidant enzyme activity and oxidative stress markers were significantly improved by N-acetylcysteine, S-methylcysteine, and their combination. Molecular docking suggested stable interactions of these compounds with antioxidant enzymes. The interaction network highlights Nrf2 as a central regulator of antioxidant genes, modulated by specific lncRNAs. Findings support the neuroprotective role of N-acetylcysteine, S-methylcysteine through activation of the Nrf2/Ho-1 pathway, modulation of long non-coding RNAs, and oxidative stress improvement in Parkinson's disease.

Image 1

•NAC and SMC regulated the expression of lncRNAs and antioxidant genes in a Parkinson's model.•Antioxidant enzyme activities and total antioxidant capacity were improved by NAC and SMC.•The Nrf2/Ho-1 pathway, as a central regulator of oxidative stress, was activated by NAC and SMC.

NAC and SMC regulated the expression of lncRNAs and antioxidant genes in a Parkinson's model.

Antioxidant enzyme activities and total antioxidant capacity were improved by NAC and SMC.

The Nrf2/Ho-1 pathway, as a central regulator of oxidative stress, was activated by NAC and SMC.