DJ-1(PARK7) (from Dekker MC et al. 2003 and Chung KK et al. 2003)
In 2001, shortly after the localization of the PARK6 locus
(Valente et al.,
2001), a second locus on chromosome 1p36, PARK7, was reported. PARK7 is ~25 centiMorgans
(cM) removed from the PARK6 locus. Linkage to the PARK7 locus was fist identified in a kindred from a genetically isolated population in the South-West of The Netherlands segregating autosomal recessive early-onset parkinsonism
(van Duijn et al.,
2001), and subsequently was confirmed in an Italian family (Bonifati et al.,
2002). In clinical features, DJ-1 parkinsonism was characterized by variable severity of disease and slow progression of symptoms, with sustained response to levodopa
treatment.
UchL1 is one of the most abundant proteins in the brain and is a family member of the
ubiquitin-proteasomal
pathway (UPP) that are responsible for degrading polyubiquitin chains back to the ubiquitin monomer
(Larsen
CN, Krantz BA, Wilkinson KD.,1998;
Wilkinson
KD. et al., 1989). The mutation was found to decrease the enzymatic activity of
UchL1, but how this is linked to PD is not known
(Leroy et al., 1998). A more recent report has shown that apart from UchL1’s hydrolase
activity, it also displays ubiquitin ligase activity, which provides further evidence that it is causally related to PD
(Liu
Y. et al., 2002).Mutations in UchL1 are rare in PD, as only two affected family members in one family have been identified in a large genome wide search
(Harhangi
BS. et al., 1999).