RNA-seq profiling of wild-type C. elegans (N2) fed with succinate (N2_Sc) against untreated control and transgenic C. elegans expressing human a-synuclein (NL5901)
Metabolites produced by human gut microbiome have a profound influence on brain health with increasing associations to Parkinson's disease pathology that lack a mechanistic insight. Using Caenorhabditis elegans model expressing human a-synuclein, we systematically tested key microbial fermentation products and identified succinate as a potent driver of pathology. As succinate administration was found to alter major PD associated pathological end-points, we further investigated the changes at transcriptional level by performing the whole worm transcriptome profiling of the wild-type strain. Through differentially expressed genes (DEGs), we examined the extent of physiological impact exerted by an exogenously administered metabolite and tried to comprehend the mechanism through which succinate generates a proteotoxic environment that promotes aggregation of alpha-synuclein in a transgenic C. elegans strain expressing human alpha-synuclein. It also helped us to identify the molecular pathways that result in mitochondrial dysfunction and substantiate our findings.
Metabolites produced by human gut microbiome have a profound influence on brain health with increasing associations to Parkinson's disease pathology that lack a mechanistic insight. Using Caenorhabditis elegans model expressing human a-synuclein, we systematically tested key microbial fermentation products and identified succinate as a potent driver of pathology. As succinate administration was found to alter major PD associated pathological end-points, we further investigated the changes at transcriptional level by performing the whole worm transcriptome profiling of the wild-type strain. Through differentially expressed genes (DEGs), we examined the extent of physiological impact exerted by an exogenously administered metabolite and tried to comprehend the mechanism through which succinate generates a proteotoxic environment that promotes aggregation of alpha-synuclein in a transgenic C. elegans strain expressing human alpha-synuclein. It also helped us to identify the molecular pathways that result in mitochondrial dysfunction and substantiate our findings.
European Bioinformatics Institute