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.

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.

Figures