Imagine treating Parkinson’s disease like planting a garden. The treatment with monosialotetrahexosylganglioside (GM1) is like planting a special seed that improves the symptoms of Parkinson’s disease (PD). But what happens to the DNA in our bodies during this treatment? Scientists wanted to find out, so they examined the DNA methylation (a fancy term for the process that changes how genes are expressed) in the blood of PD patients who received GM1 therapy. They found 235 positions in the DNA that were significantly changed by this therapy! Some genes became more methylated (which can turn down their activity), while others became less methylated (which can turn up their activity). Interestingly, when they looked closer at these genes, they discovered that some of them are involved in a pathway called the dopaminergic synapse pathway, which is important for controlling movement and is affected in PD. One gene in particular, called CREB5, became hypermethylated, meaning it had extra methyl groups added to it. This alteration was associated with decreased expression of CREB5 and improvements in motor symptoms. These findings suggest that GM1 therapy may work by modifying the methylation pattern of certain genes, like CREB5, to improve symptoms of PD. To learn more about this fascinating study and its potential implications for treating PD, check out the full article!

IntroductionThe treatment with monosialotetrahexosylganglioside (GM1) improves the symptoms of Parkinson’s disease (PD). The alteration of DNA methylation in the blood was examined to investigate epigenetic modification by GM1 treatment.MethodsAfter a 28-day continuous intravenous infusion of GM1 (100mg), the motor and non-motor symptoms were evaluated by UPDRS III, Mini-mental state examination (MMSE) scores, FS-14, SCOPA-AUT, and PDQ-8. Moreover, blood samples were collected and PBMC was isolated. Genome-wide DNA methylation was performed by an 850K BeadChip. RNA levels and apoptosis were examined by RT-PCR and flow cytometry in rotenone-based cell models. The CREB5 plasmid was transfected by electroporation into SH-SY5Y cells. We also identified 235 methylation variable positions achieving genome-wide significance in 717558 differentially methylated positions (DMPs) (P = 0.0003) in comparison of pre-treatment with post-treatment measurements (statistical analysis paired-samples t-test).ResultsBy searching the Gene Expression Omnibus (GEO) dataset and GWAS, 23 methylation variable positions were screened. Moreover, there are 7 hypomethylated methylation variable positions correlated with the scores of motor symptoms (UPDRS III scale). According to KEGG pathways enrichment analysis, the methylated genes CACNA1B (hypomethylated), CREB5 (hypermethylated), GNB4 (hypomethylated), and PPP2R5A (hypomethylated) were enriched in the dopaminergic synapse pathway. Pretreated with GM1 (80 μM) for 1 h, cell apoptosis and impaired neurite outgrowth were inhibited in rotenone-induced PD cell models. The RNA expression of CREB5 was increased in rotenone-treated SH-SY5Y cells. GM1 treatment decreased rotenone-induced CREB5 gene expression. The enhancement of CREB5 gene expression suppressed the protective role of GM1 in rotenone-induced cell apoptosis.DiscussionThe application of GM1 improves the motor and non-motor symptoms of PD associated with the decreased CREB5 expression and the hypermethylation of CREB5.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=120582t, identifier ChiCTR2100042537.

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