NeuralCipher Research overview
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Abstract Background Initial targeted assessments revealed a discordance in α-synuclein (α-syn) homeostasis in Parkinson's disease (PD), characterized by elevated plasma protein levels despite downregulated SNCA mRNA in peripheral blood mononuclear cells (PBMCs). This was accompanied by a significant downregulation of the m6A methyltransferase METTL14 and the reader proteins YTHDF1/3. Methods To decode the systemic epitranscriptomic landscape, we performed integrated MeRIP-seq and RNA-seq profiling. Results Our analysis uncovered widespread m6A methylome remodeling in PD PBMCs, with differentially methylated genes predominantly enriched in immune-response pathways, including neutrophil activation, Th17 cell differentiation, and MHC class II antigen presentation. Conjoint multi-omics analysis further identified a coordinated hypermethylation and upregulation of key neurodegeneration-associated transcripts—specifically NEFL , LCN2 , and CHI3L1 —implicating aberrant m6A modification in altered transcript stability. Conclusions Collectively, this study provides a comprehensive map of the PBMC m6A epitranscriptome in PD, highlighting an association between METTL14 downregulation and peripheral immune alterations, and offering a foundational resource for future investigations into non-invasive epitranscriptomic biomarkers.
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