ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90 chaperone complex for proteasomal degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025Review
- High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development of quantitative high-throughput screening assays to identify, validate, and optimize small-molecule stabilizers of misfolded β-glucocerebrosidase with therapeutic potential for Gaucher disease and Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson's Disease Research.Journal of Parkinson's disease · 2024Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- The Biology of Lysosomes: From Order to Disorder.Biomedicines · 2023Review
- Identification of Isocitrate Dehydrogenase 2 (IDH2) Mutation in Carotid Body Paraganglioma.Frontiers in endocrinology · 2021Article
- Targeting NRF2-Governed Glutathione Synthesis forCancers · 2020Article
- Mutant-selective topologic conversion facilitates selective degradation of a pathogenic prion isoform.Cell death and differentiation · 2020Article
- Blockade of Glutathione Metabolism inMolecular cancer therapeutics · 2020Article
- Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease.Neurobiology of disease · 2019Review
- The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase.EBioMedicine · 2018Article
- 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
- A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments.International journal of molecular sciences · 2017Review
- Expanding role of molecular chaperones in regulating α-synuclein misfolding; implications in Parkinson's disease.Cellular and molecular life sciences : CMLS · 2017Review
- Progress and potential of non-inhibitory small molecule chaperones for the treatment of Gaucher disease and its implications for Parkinson disease.Expert review of proteomics · 2016Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
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 mutants with subsequent targeting of GCase mutant peptides to degradation mechanisms such as VCP and the 26S proteasome. Inhibition of Hsp27 not only increased the quantity of enzyme but also enhanced GCase activity in fibroblasts derived from patients with Gaucher disease. These findings provide insight into a possible therapeutic strategy for protein misfolding diseases by correcting chaperone binding and altering subsequent downstream patterns of protein degradation.
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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.