BACKGROUND: α-Synuclein aggregates in Lewy bodies and plays a central role in 
the pathogenesis of a group of neurodegenerative disorders, known as 
"Synucleinopathies", including Parkinson's disease. Parkin mutations result in 
loss of parkin E3-ubiquitin ligase activity and cause autosomal recessive early 
onset parkinsonism.
RESULTS: We tested how these two genes interact by examining the effects of 
parkin on post-translational modification of α-Synuclein in gene transfer animal 
models, using a lentiviral gene delivery system into the striatum of 2-month old 
male Sprague Dawley rats.Viral expression of wild type α-Synuclein caused 
accumulation of α-Synuclein and was associated with increased cell death and 
inflammation. α-Synuclein increased PLK2 levels and GSK-3β activity and 
increased the levels of phosphorylated α-Synuclein and Tau. Parkin co-expression 
reduced the levels of phosphorylated α-Synuclein and attenuated cell death and 
inflammation. Parkin reduced PLK2 levels and increased PP2A activation.
CONCLUSIONS: These data suggest that parkin reduces α-Synuclein levels and 
alters the balance between phosphatase and kinase activities that affect the 
levels of phosphorylated α-Synuclein. These results indicate novel mechanisms 
for parkin protection against α-Synuclein-induced toxicity in PD.