Transcriptomics analyses of the LRRK2 protein interactome reveal distinct molecular signatures for sporadic and LRRK2 Parkinson’s Disease

Abstract

AbstractMutations in theLRRK2gene are an important genetic cause for familial Parkinson’s Disease (LRRK2-PD) and clinical trials are ongoing to evaluate the benefits associated with the therapeutical reduction of LRRK2 kinase activity. In this study, we aimed at modelling the molecular milieu surrounding LRRK2 and describe the changes that occur during disease with the aim of contrasting and comparing sporadic PD and LRRK2-PD. We analysed the molecular expression profiles (whole blood mRNA) of LRRK2’s protein interactors in the sporadic vs familial PD conditions and found interesting differences between the 2 scenarios. Our results showed that LRRK2 interactors not only presented different alterations in expression levels in sporadic and familial PD while compared to controls; they also exhibited distinct co-expression behaviours in the 2 PD conditions. These results suggest that, albeit being classified as the same disease based on clinical features, LRRK2-PD and sporadic PD show significant differences from a molecular perspective.