Proteomics analysis of lysosomes and whole cell lysates from H4 cellsLysosome, H4, glucocerebrosidase

Studies have shown that the majority of Parkinson's disease patients have at least one putative damaging variant in a lysosomal storage disorder gene (60%) and in about 10% of sporadic PD subjects, the disease is associated with mutations in GBA1, a gene coding for glucocerebrosidase, a lysosomal hydrolase. However, the precise cellular and lysosome-specific alterations upon loss of glucocerebrosidase are not established. The aim of this study is to characterize the proteome-wide changes at the cellular and lysosomal level in H4 cells upon loss of the GBA gene. Moreover, we tested if reinstating glucocerebrosidase activity by treating cells with our in-house GCase-BS (glucocerebrosidase-brain shuttle) can revert these changes, both at the cellular and lysosomal level.