Abstract
Parkinson disease (PD) is one of the most common neurodegenerative diseases. The genetic mutations in Leucine-rich repeat kinase 2 (LRRK2) have been identified as the most common cause of sporadic and familial PD. Recently, mitochondrial dysfunction has been implicated as the cause of the death of DA neurons in PD. The relationship between human LRRK2 and mitochondrial function is still unknown. Here, we express human wild-type LRRK2 and its mutant G2019S in DA neurons of Drosophila brain and characterize superoxide dismutases (SODs) which is an important mitochondrial antioxidant enzyme. We find that human wild-type LRRK2 affects the level of mitochondrial SOD2 to constrain the age-dependent increase of oxidative stress but its mutation LRRK2 G2019S does not. In contrast, in its loss of function mutants of Drosophila homolog of LRRK2, called dLRRK, we find that it decreases the level of SOD2 and increase oxidative stress. We also characterize the level of SODs in expressing LRRK2 flies under different environmental toxins. Finally, we co-express LRRK2 and Tau in fly eye system. Importantly, wild-type LRRK2 reduces the phosphorylation of Tau. Taken together, it seems that human LRRK2 plays a novel protective role to reduce mitochondrial oxidative stress.