Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase
نویسندگان
چکیده
منابع مشابه
Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein ...
متن کاملAmbroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study
OBJECTIVE Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of ...
متن کاملAmbroxol effects in glucocerebrosidase and α‐synuclein transgenic mice
OBJECTIVE Gaucher disease is caused by mutations in the glucocerebrosidase 1 gene that result in deficiency of the lysosomal enzyme glucocerebrosidase. Both homozygous and heterozygous glucocerebrosidase 1 mutations confer an increased risk for developing Parkinson disease. Current estimates indicate that 10 to 25% of Parkinson patients carry glucocerebrosidase 1 mutations. Ambroxol is a small ...
متن کاملMutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90 chaperone complex for proteasomal degradation.
Gaucher disease is caused by mutations of the GBA1 gene, which encodes the lysosomal anchored gluococerebrosidase (GCase). GBA1 mutations commonly result in protein misfolding, abnormal chaperone recognition, and premature degradation, but are less likely to affect catalytic activity. In the present study, we demonstrate that the Hsp90/HOP/Cdc37 complex recruits Hsp27 after recognition of GCase...
متن کاملBicyclic (galacto)nojirimycin analogues as glycosidase inhibitors: effect of structural modifications in their pharmacological chaperone potential towards β-glucocerebrosidase.
A molecular-diversity-oriented approach for the preparation of bicyclic sp(2)-iminosugar glycomimetics related to nojirimycin and galactonojirimycin is reported. The synthetic strategy takes advantage of the ability of endocyclic pseudoamide-type atoms in five-membered cyclic iso(thio)ureas and guanidines to undergo intramolecular nucleophilic addition to the masked carbonyl group of monosaccha...
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ژورنال
عنوان ژورنال: Blood Cells, Molecules, and Diseases
سال: 2013
ISSN: 1079-9796
DOI: 10.1016/j.bcmd.2012.10.007