Post-transcriptional regulation of Alpha-synuclein and link to Parkinson's disease

The role of RNA processing in the pathogenesis of neurodegenerative diseases is still poorly understood. α-synuclein (SNCA) is a presynaptic neuronal protein known as the major component of Lewy bodies, the pathological hallmark of Parkinson’s disease (PD). Recent evidence suggests a link between the pathogenesis of PD and the expression of SNCA mRNA isoforms with 3’ untranslated region (3’UTR) of different lengths. The purpose of my doctoral studies was the discovery of RNA-binding proteins (RBPs) regulating SNCA at the post-transcriptional level. Using computational and experimental approaches, I identified a number of trans-acting elements that physically interact with SNCA and potentially control its metabolism. I especially focused on the characterization of two RBPs, ELAVL1 and TIAR, and showed their implication in SNCA mRNA stability and translation efficiency. These two factors might play important roles in the maintenance of α-synuclein level and functionality in physiological and pathological conditions.