Parkinson disease (PD) is a chronic and neurodegenerative disorder characterised by a loss neurons that produce dopamine, a hormonal transmitter responsible for the coordination of body movements. It is estimated that 1 in 500 worldwide suffers from PD.1 The number of new cases increases with age for both males and females, with peaks between the ages of 70 and 79.2 As the world faces an aging population, there is a need to develop efficient treatments of PD in particular at its early stage. For this reason, the understanding of the molecular mechanisms that initiate PD is crucial.
Although the causes of most PD are unknown, mutations in the leucine rich repeat kinase 2 (LRRK2) gene were found to be highly correlated to the familial forms of PD. The most common mutation is a glycine to serine amino acid substitution at position 2019 of the kinase domain of LRRK2, which increases its activity3 and modifies protein translation.4In vitro and in vivo studies have shown that the ribosomal protein S15 to be a substrate of LRRK2, which upon phosphorylation causes translation dysfunction and subsequent neurodegeneration.5
Our aim is to understand the connections between LRRK2 mutation, S15 phosphorylation and modifications in translation. We employ molecular biology methods and a range of biophysical techniques to investigate the biochemistry and structure of LRRK2 and S15 in order to provide knowledge for the development of new pharmaceutical compounds.