oa Genetic and Epigenetic Investigations of SNCA in Parkinson's Disease

Parkinson's disease (PD) (OMIM168600) is the second most common age-related neurodegenerative disorder worldwide with a prevalence of more than 1% in people over 65 years old. The major hallmark of PD brain change is the formation of Lewy bodies, which are mainly composed of a protein called alpha-synuclein (encoded by the SNCA gene), aggregated together with other proteins.

Genetic variants of SNCA have been reported to be involved in both familial as well as sporadic cases of PD. Many of these variants result in the over-expression of the encoded protein making it prone to aggregation.

This report describes investigation of methylation of the two CpG islands in SNCA in brain samples from PD patients.

Fifty three DNA samples were made from cerebellum of PD brains, to add to 268 existing DNA samples. In the first part of the study, confirmation of suspected monogenic PD mutations was carried out using PCR and sequencing. However, no mutation was detected. Possible reasons for the discrepancy between predicted and observed results are discussed. In addition, 250 PD cases were screened for three monogenic mutations in SNCA using commercial service and found that none of these cases have the mutations.

In the second part of the study, DNA methylation of two SNCA CpG islands was assessed in seven different brain regions of ten PD cases using bisulfite sequencing. No significant difference was observed in DNA methylation of CpG 1, as well as CpG 2, when compared to the studied brain regions.

Genetic and epigenetic studies on PD can help to provide better understanding of the mechanisms underlying the disease and its progression, enhancing our ability to discover and develop better treatment options for the future.