biostudies-arrayexpressAamir NazirCaenorhabditis eleganshttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-15794Metabolites 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 α-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.biostudies-arrayexpressSample Collection - Young adult worms were harvested and washed with M9 buffer and 0.2 % diethyl pyrocarbonate (DEPC) treated water, 3 times each, for removing any adherent bacteria and to inactivate RNase enzymes. QIAzol Lysis Reagent (1000μl) was added and worms were homogenized using pestle.Nucleic Acid Extraction - RNA was isolated using QIAzol Lysis Reagent and miRNeasy Mini Kit. 500ng of total RNA was used for the construction of sequencing libraries.Library Construction - The Libraries were made using KAPA RNA HyperPrep Kit Illumina® Platforms following manufacturer's protocol.Sequencing - Fastp filtration tool was used to filter high quality reads form raw data.A cut-off of 30 was set for the quality phred score and only high-quality reads with minimum read length 70 were retained.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - Alignment was performed by HISAT2 with default parameters. The read alignments were subjected to reference-based assembly using Stringtie. The transcripts were assembled and quantified from the aligned reads for each sample using Stringtie (v2.1.4) and the expression read counts of the transcripts were normalized by calculating Fragments Per Kilobase of transcript per Million mapped reads (FPKM).MetabolomicsUnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq 6000RNA-seq of coding RNACaenorhabditis elegansGut Microbiota–Derived Succinate Links Proteostasis Collapse to α-Synuclein Pathology and AgingMahmood AkbarAamir NazirMahmood Akbar, Sakshi Yadav, Anam Naseer, Rohil Hameed, Arunabh Sarkar, and Aamir NazirfalseRNA-seq profiling of wild-type C. elegans (N2) fed with succinate (N2_Sc) against untreated control and transgenic C. elegans expressing human α-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 α-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.2026-04-21T00:00:00Z2026-04-21T01:03:32.129Z2025-10-21T12:50:00.293ZE-MTAB-15794ERP182574EFO_0002944EFO_0004170EFO_0005518EFO_0003816EFO_0003738EFO_0004184