UCH-L1 (PARK5) (from Dekker MC et al. 2003 and Chung KK et al. 2003)
In 1998, the I93M mutation in the ubiquitin C-terminal hydroxylase L1 (UCH-L1) gene on chromosome 4p14 was identified in a family of German descent in which Parkinson's disease was inherited in an autosomal dominant fashion (Leroy et al., 1998). The clinical phenotype in these siblings consisted of dopa-responsive parkinsonism, resembling idiopathic Parkinson's disease. Mutations in the UCH-L1 enzyme reduce its catalytic activity in vitro, therefore possibly leading to a tendency for various protein metabolites to aggregate (Saigoh et al., 1999). In immunofluorescence studies, Lewy bodies stained positive for UCH-L1, suggesting it also contributes to the ubiquitin-proteasome pathway implicated in α-synuclein- and parkin-linked parkinsonism (Leroy et al., 1998).