ArticleMolecular genetics and metabolism2012
Pharmacological chaperones facilitate the post-ER transport of recombinant N370S mutant β-glucocerebrosidase in plant cells: evidence that N370S is a folding mutant.
Article in Molecular genetics and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial.JAMA neurology · 2020Trial
- 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
- Functional Analysis of HumanCells · 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
- Identification of GM1-Ganglioside Secondary Accumulation in Fibroblasts from Neuropathic Gaucher Patients and Effect of a Trivalent Trihydroxypiperidine Iminosugar Compound on Its Storage Reduction.Molecules (Basel, Switzerland) · 2024Article
- Patient reported outcome measures in a large cohort of patients with type 1 Gaucher disease.Orphanet journal of rare diseases · 2020Article
- Article
- Pharmacotherapy of Gaucher Disease: Current and Future Options.P & T : a peer-reviewed journal for formulary management · 2018Article
- Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Stabilization of Glucocerebrosidase by Active Site Occupancy.ACS chemical biology · 2017Article
- The contribution of mutant GBA to the development of Parkinson disease in Drosophila.Human molecular genetics · 2016Article
- 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
- 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
- Gaucher iPSC-derived macrophages produce elevated levels of inflammatory mediators and serve as a new platform for therapeutic development.Stem cells (Dayton, Ohio) · 2014Article
- Glucocerebrosidase is shaking up the synucleinopathies.Brain : a journal of neurology · 2014Review
- Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase.Plant signaling & behavior · 2014Article
- Insights into mucopolysaccharidosis I from the structure and action of α-L-iduronidase.Nature chemical biology · 2013Article
- Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase.Blood cells, molecules & diseases · 2013Article
- Gaucher disease: Progress and ongoing challenges.Molecular genetics and metabolismReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Gaucher disease is a prevalent lysosomal storage disease in which affected individuals inherit mutations in the gene (GBA1) encoding lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent disease-causing mutations in humans is a N370S missense mutation in the GCase protein. As part of a larger endeavor to study the fate of mutant human proteins expressed in plant cells, the N370S mutant protein along with the wild-type- (WT)-GCase, both equipped with a signal peptide, were synthesized in transgenic tobacco BY2 cells, which do not possess lysosomes. The enzymatic activity of plant-recombinant N370S GCase lines was significantly lower (by 81-95%) than that of the WT-GCase lines. In contrast to the WT-GCase protein, which was efficiently secreted from tobacco BY2 cells, and detected in large amounts in the culture medium, only a small proportion of the N370S GCase was secreted. Pharmacological chaperones such as N-(n-nonyl) deoxynojirimycin and ambroxol increased the steady-state mutant protein levels both inside the plant cells and in the culture medium. These findings contradict the assertion that small molecule chaperones increase N370S GCase activity (as assayed in treated patient cell lysates) by stabilizing the enzyme in the lysosome, and suggest that the mutant protein is impaired in its ability to obtain its functional folded conformation, which is a requirement for exiting the lumen of the ER.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.