Characterization of D. melanogaster models for LRRK2-linked Parkinson’s disease study

Parkinson’s disease (PD) is the second most prevalent cause of dementia and it is mainly characterized by the motor symptoms and loss of dopaminergic neurons of Substantia Nigra (SN). Most of the cases are sporadic (iPD), although a significant percentage of cases are caused by Mendelian gene mutations, valuable to characterize new features. Mutations in LRRK2, a protein with kinase/GTPase activity, are the most common genetic cause of familial PD. Furthermore, pathogenic mutations in LRRK2 such as G2019S, the most common one or R1441G, found in a cluster of Basque families, lead to a hyperactivation of the kinase activity causing PD. In this study, we have performed a functional-phenotypical characterization of some PD Drosophila models (hLRRK2WT; hLRRK2G2019S; hLRRK2R1441C; hLRRK2R1441G; dLrrk2WT) in order to select few of them, to find new therapeutic targets and identify the suitability of each model for Drug Discovery projects.