ArticleProceedings of the National Academy of Sciences of the United States of America2010
Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025Review
- Variant-specific effects of GBA1 mutations on dopaminergic neuron proteostasis.Journal of neurochemistry · 2024Article
- Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson's Disease Research.Journal of Parkinson's disease · 2024Article
- Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities.Journal of lipid research · 2020Article
- Exploring genetic modifiers of Gaucher disease: The next horizon.Human mutation · 2018Review
- Molecular regulations and therapeutic targets of Gaucher disease.Cytokine & growth factor reviews · 2018Review
- D409H GBA1 mutation accelerates the progression of pathology in A53T α-synuclein transgenic mouse model.Acta neuropathologica communications · 2018Article
- Molecular docking and ADME properties of bioactive molecules against human acid-beta-glucosidase enzyme, cause of Gaucher's disease.In silico pharmacology · 2018Article
- Dermal fibroblasts from patients with Parkinson's disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations.F1000Research · 2017Article
- Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models.Scientific reports · 2016Article
- Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling.Oncotarget · 2016Article
- Mutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90 chaperone complex for proteasomal degradation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity.PloS one · 2015Article
- Parkin-mediated ubiquitination of mutant glucocerebrosidase leads to competition with its substrates PARIS and ARTS.Orphanet journal of rare diseases · 2014Article
- Glucocerebrosidase is shaking up the synucleinopathies.Brain : a journal of neurology · 2014Review
- Celastrol increases glucocerebrosidase activity in Gaucher disease by modulating molecular chaperones.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- An innovative approach to the treatment of Gaucher disease and possibly other metabolic disorders of the brain.Journal of inherited metabolic disease · 2013Review
- Histone deacetylase inhibitors increase glucocerebrosidase activity in Gaucher disease by modulation of molecular chaperones.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism.Critical reviews in oncogenesis · 2013Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Gaucher disease (GD), the most common lysosomal storage disorder of humans, is caused by mutations in the gene coding for the enzyme glucocerebrosidase (GCase). Clinical manifestations vary among patients with the three types of GD, and phenotypic heterogeneity occurs even among patients with identical mutations. To gain insight into why phenotypic heterogeneity occurs in GD, we investigated mechanisms underlying the net loss of GCase catalytic activity in cultured skin fibroblasts derived from patients with the three types of GD. The findings indicate that the loss of catalytic activity of GCase correlates with its quantitative reduction, rather than a decrease in functional capacity of mutant enzyme. Use of a proteasome inhibitor, lactacystin, resulted in increased expression of GCase, suggesting a mechanism of protein degradation in GD. Furthermore, reduced binding of GCase to TCP1 ring complex (TRiC), a regulator of correct protein folding, may result in defective maturation of nascent GCase in GD cells. Additionally, increased interaction between GCase and c-Cbl, an E3 ubiquitin ligase, may be involved in the degradation and loss of GCase in GD. The findings suggest that specific molecular mediators involved in GCase maturation and degradation could be responsible for phenotypic variation among patients with the same genotypes and that these mediators could be therapeutically targeted to increase GCase activity in patients with GD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.