DNA methylation changes associated with Parkinson's disease in SNCA

Parkinson's disease (PD) is a progressive neurodegenerative disorder influenced by both genetic and epigenetic mechanisms. Among these mechanisms, DNA methylation has emerged as a key regulatory process affecting gene expression without altering the DNA sequence. The synuclein alpha (SNCA) gene is a well-established contributor to Parkinson's disease pathogenesis, yet the extent and consistency of its methylation changes remain unclear. This scoping review aimed to map and summarise existing evidence on DNA methylation changes associated with PD in the SNCA gene. A scoping review methodology guided by Arksey and O'Malley's framework was employed. Relevant studies were identified through systematic searches of electronic databases. Eligible studies included those investigating DNA methylation patterns in SNCA in PD patients using post-mortem brain tissue or peripheral blood samples. Data were extracted and analysed descriptively to summarise study characteristics and key findings. A total of 18 studies were included. The findings demonstrated variable DNA methylation patterns; studies generally reported either hypomethylated patterns or no significant DNA methylation differences. The review highlights the potential role of DNA methylation in PD pathogenesis and its potential as a diagnostic or prognostic biomarker. However, inconsistencies across studies and limited evidence underscore the need for larger, standardised, and longitudinal studies to better understand the temporal dynamics and clinical relevance of these epigenetic modifications.