Defective glucocerebrosidase in GBA1 mutant Parkinson's disease fibroblasts is rescued by chemical chaperone ambroxol through modulation of lysosomal factors

Introduction: Heterozygous mutations in GBA1 gene, encoding for lysosomal enzyme glucocerebrosidase (GCase), are a major risk factor for sporadic Parkinson's disease (PD) [1]. Defective GCase has been recently reported in fibroblasts of GBA1-mutant PD patients and pharmacological chaperone ambroxol has been shown to correct such defect [2]. A number of endogenous elements support GCase activity, especially transporter and lysosomal receptor LIMP2 and activator saposin (Sap) C [3].