Missense mutations in leucine-rich repeat kinase 2 (LRRK2)/Dardarin gene, the 
product of which encodes a kinase with multiple domains, are known to cause 
autosomal dominant late onset Parkinson's disease (PD). In the current study, we 
report that the gene product LRRK2 directly phosphorylates the forkhead box 
transcription factor FoxO1 and enhances its transcriptional activity. This 
pathway was found to be conserved in Drosophila, as the Drosophila LRRK2 homolog 
(dLRRK) enhanced the neuronal toxicity of FoxO. Importantly, FoxO mutants that 
were resistant to LRRK2/dLRRK-induced phosphorylation suppressed this 
neurotoxicity. Moreover, we have determined that FoxO targets hid and bim in 
Drosophila and human, respectively, are responsible for the LRRK2/dLRRK-mediated 
cell death. These data suggest that the cell death molecules regulated by FoxO 
are key factors during the neurodegeneration in LRRK2-linked PD.