ArticleBiochimica et biophysica acta2014
A thermodynamic assay to test pharmacological chaperones for Fabry disease.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations.International journal of molecular sciences · 2016Pooled it
- Human in vitro models for Fabry disease: new paths for unravelling disease mechanisms and therapies.Journal of translational medicine · 2024Review
- Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease.International journal of molecular sciences · 2023Article
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- β-Glucose-1,6-Bisphosphate Stabilizes Pathological Phophomannomutase2 Mutants In Vitro and Represents a Lead Compound to Develop Pharmacological Chaperones for the Most Common Disorder of Glycosylation, PMM2-CDG.International journal of molecular sciences · 2019Article
- Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.BMC bioinformatics · 2018Article
- In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease.Journal of visualized experiments : JoVE · 2017Article
- E-Learning for Rare Diseases: An Example Using Fabry Disease.International journal of molecular sciences · 2017Article
- Effects of ligand binding on the stability of aldo-keto reductases: Implications for stabilizer or destabilizer chaperones.Protein science : a publication of the Protein Society · 2016Article
- Article
- Looking for protein stabilizing drugs with thermal shift assay.Drug testing and analysis · 2015Article
- Taming molecular flexibility to tackle rare diseases.Biochimie · 2015Article
- Using pharmacological chaperones to restore proteostasis.Pharmacological research · 2014Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe majority of the disease-causing mutations affect protein stability, but not functional sites and are amenable, in principle, to be treated with pharmacological chaperones. These drugs enhance the thermodynamic stability of their targets. Fabry disease, a disorder caused by mutations in the gene encoding lysosomal alpha-galactosidase, represents an excellent model system to develop experimental protocols to test the efficiency of such drugs.
methodsThe stability of lysosomal alpha-galactosidase under different conditions was studied by urea-induced unfolding followed by limited proteolysis and Western blotting.
resultsWe measured the concentration of urea needed to obtain half-maximal unfolding because this parameter represents an objective indicator of protein stability.
conclusionsUrea-induced unfolding is a versatile technique that can be adapted to cell extracts containing tiny amounts of wild-type or mutant proteins. It allows testing of protein stability as a function of pH, in the presence or in the absence of drugs. Results are not influenced by the method used to express the protein in transfected cells. GENERAL SIGNIFICANCE: Scarce and dispersed populations pose a problem for the clinical trial of drugs for rare diseases. This is particularly true for pharmacological chaperones that must be tested on each mutation associated with a given disease. Diverse in vitro tests are needed. We used a method based on chemically induced unfolding as a tool to assess whether a particular Fabry mutation is responsive to pharmacological chaperones, but, by no means is our protocol limited to this disease.
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