Since a substitution of serine by tyrosine at codon 18, exon 3 (S18Y polymorphism) of the UCH-L1 gene exhibits a protective effect against the development of degenerative disease such as sporadic Parkinson's disease (PD) in several different ethnic groups, we hypothesized that UCH-L1 gene S18Y polymorphism may have that same effect on the pathologic process of AD.
Taken together, these results suggest that further studies of altered UCH-L1 hydrolase function may provide new insights into a possible common pathogenic mechanism between familial and sporadic Parkinson's disease.
We propose that aberrant interactions of UCH-L1 variants with CMA machinery, at least partly, underlie the pathogenesis of I93MUCH-L1-associated PD, and possibly of sporadic PD.
A protective effect of a UCH-L1 variant, S18Y, was suggested since the common variant was found to be inversely associated with sporadic Parkinson's disease (PD).
A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C-terminal hydrolase-L1 gene is associated with a reduced risk of sporadic Parkinson's disease in a Japanese population.
We conclude that the S18Y variant of UCH-L1 confers a novel antioxidant function that is not present in the WT form and that this function may underlie the protective effects of this variant in certain PD populations.