Lack of direct role of parkin in the steady-state level and aggregation of α-synuclein and the clearance of pre-formed aggregates

Mutations in parkin and α-synuclein (α-syn) are linked to heritable forms of Parkinson's disease (PD). Recently, it has been shown that parkin mitigates α-syn-induced neuronal cell death in animal and tissue culture models, suggesting that there is a functional relationship between these two proteins. Although the mechanism by which parkin protects cells from α-syn-induced cytotoxicity remains elusive, it is tempting to speculate that parkin might directly regulate the normal metabolism and aggregation of α-syn. In the current study, we show that neither the suppression of endogenous parkin expression nor ectopic overexpression affects the steady-state levels of endogenous α-syn expression, overall aggregation of this protein, or breakdown of pre-formed aggregates in human neuroblastoma cells. These results suggest that parkin is not directly involved in the metabolism of α-syn, its aggregation, or the clearance of pre-formed aggregates.