PARK6 (PINK1)

The PARK6 locus was first identified in a large Italian family exhibiting autosomal recessive, young onset parkinsonism and subsequently confirmed in other European families (Valente et al., 2001; Valente et al., 2002). Mutations in the gene for PTEN-induced kinase 1 (PINK1) were ultimately associated with the PARK6 locus (Valente et al., 2004). Clinically, PARK6-related PD is characterized by earlier age of onset and slower disease progression (Gasser, 2009).

PINK1 is a serine/threonine kinase present in mitochondria, and identified mutations associated with PD likely disrupt kinase function (Yang et al., 2009). The relationship between PINK1, mitochondria and oxidative stress lends credence to the hypothesis that oxidative damage plays an important role in PD pathogenesis. Interactions between PINK1, parkin, DJ-1 and Omi/HtrA2 have been reported, suggesting some pathogenic links between oxidative stress and aggregation hypotheses (Yang et al., 2006; Tan and Dawson, 2006; Plun-Favreau et al., 2007; Shiba et al., 2009; Um et al., 2009; Xiong et al., 2009).