Decreased activities of lysosomal acid alpha-D-galactosidase A in the leukocytes of sporadic Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease that affects aged people. Although a number of genes have been linked to familial PD, the genetic causes of sporadic PD that accounts for 90% of all PD cases remain unclear. Accumulating evidence has demonstrated that alpha-synuclein aggregation is essential to the pathogenesis of PD. Recent studies suggest that autophagic-lysosomal system play major roles in the process of alpha-synuclein aggregation. We hypothesized that lysosomal acid hydrolases may be involved in the alpha-synuclein degradation and aggregation. In this study, we examined the activities of 11 lysosomal acid hydrolases in peripheral blood leukocytes of 38 sporadic PD patients and 258 age- and sex-matched healthy controls. The activities of alpha-D-galactosidase A were significantly decreased in sporadic PD patients, compared to age- and sex-matched controls. In contrast, no significant differences of the activities of other 10 lysosomal acid hydrolases was observed. This initial study suggests that decreased activities of lysosomal alpha-D-galactosidase A in the central nervous system may be involved in the degradation and aggregation of alpha-synuclein protein and contribute to the pathogenesis of sporadic PD as a risk factor.