Glucosylceramidase beta (GBA) (GBA)

Glucosylceramidase beta (GBA), commonly known as beta-glucocerebrosidase, is a lysosomal hydrolase that catalyzes the breakdown of glucosylceramide into glucose and ceramide [1, 3]. This enzyme is essential for sphingolipid metabolism and the maintenance of the skin's permeability barrier [3]. Mutations in the GBA1 gene, most notably the N370S variant, lead to Gaucher disease, a lysosomal storage disorder characterized by the accumulation of glucosylceramide in macrophages, resulting in hepatosplenomegaly, anemia, and bone disease [7, 11]. The N370S mutation is the most common pathogenic variant and is primarily associated with the non-neuronopathic Type 1 form of the disease [4, 13]. Furthermore, GBA mutations are the most significant genetic risk factor for Parkinson's disease and Dementia with Lewy bodies, where reduced enzyme activity is thought to promote the aggregation of alpha-synuclein [5, 9, 11]. Therapeutic approaches include enzyme replacement therapy (ERT) with recombinant GCase, substrate reduction therapy (SRT) to limit lipid synthesis, and pharmacological chaperones designed to stabilize mutant proteins like N370S to ensure their proper delivery to the lysosome [7, 13, 16].

Other names

Beta-glucocerebrosidaseAcid beta-glucosidaseGCaseGlucosylceramidase beta 1GBA1AlgluceraseGCBGLUC

Enzyme replacement therapy, Substrate reduction therapy, Pharmacological chaperone, Enzyme activation [7, 13, 16]