Glucocerebrosidases(GCases)catalyze the hydrolysis ofβ-glucoceremides andβ-glucosphingosines to produce glucose and ceramide or sphingosine,respectively.In humans,GCase is encoded by GBA1 which is widely and abundan...Glucocerebrosidases(GCases)catalyze the hydrolysis ofβ-glucoceremides andβ-glucosphingosines to produce glucose and ceramide or sphingosine,respectively.In humans,GCase is encoded by GBA1 which is widely and abundantly expressed and localized in lysosomal membranes,while GBA2 encodes a microsomal-β-glucosidase[1].Loss-of-function mutations in GBA1 result in accumulation of glucoceramides or glucosphingosines and underlie Gaucher’s disease(GD),a lysosomal storage disease characterized by anemia,enlarged spleen and liver,and skeletal disorders[2,3].The most common GBA1 N370S mutant retains some residual activity while homozygosity results in a range of outcomes from mild symptoms to severe disease[4].Specific GBA1 mutations are the highest known genetic risk factors(odds ratio>5)for Parkinson’s disease(PD)[5].Nonetheless,knowledge of how GCase functional loss can increase PD risk is limited due to the lack of animal models[6].In this study,we identified the gene encoding GCase in C.展开更多
基金supported in part by the Faculty of Health Sciences,University of Macao and National Natural Science Foundation of China(32400781).
文摘Glucocerebrosidases(GCases)catalyze the hydrolysis ofβ-glucoceremides andβ-glucosphingosines to produce glucose and ceramide or sphingosine,respectively.In humans,GCase is encoded by GBA1 which is widely and abundantly expressed and localized in lysosomal membranes,while GBA2 encodes a microsomal-β-glucosidase[1].Loss-of-function mutations in GBA1 result in accumulation of glucoceramides or glucosphingosines and underlie Gaucher’s disease(GD),a lysosomal storage disease characterized by anemia,enlarged spleen and liver,and skeletal disorders[2,3].The most common GBA1 N370S mutant retains some residual activity while homozygosity results in a range of outcomes from mild symptoms to severe disease[4].Specific GBA1 mutations are the highest known genetic risk factors(odds ratio>5)for Parkinson’s disease(PD)[5].Nonetheless,knowledge of how GCase functional loss can increase PD risk is limited due to the lack of animal models[6].In this study,we identified the gene encoding GCase in C.
