ReviewJournal of inherited metabolic disease2014
Innovative strategies to treat protein misfolding in inborn errors of metabolism: pharmacological chaperones and proteostasis regulators.
Review in Journal of inherited metabolic disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 116 citations in OpenAlex.
- Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2.International journal of molecular sciences · 2026Article
- The Achilles Heel of Protein Biochemistry: Insolubility of Recombinant Proteins-A Case Study About Producing a Rice Enzyme.International journal of molecular sciences · 2025Article
- Iron Ions Increase the Thermal Stability In Vitro and Activity In Vivo of the 447R Mutant Form of Mouse Tryptophan Hydroxylase 2.International journal of molecular sciences · 2025Article
- Cell-Based Small-Molecule Screening Identifying Proteostasis Regulators Enhancing Factor VIII Missense Mutant Secretion.Biomolecules · 2025Article
- Comparison of the Effects of Tetrahydrobiopterine, L-Tryptophan, and Iron Ions on the Thermal Stability of Wild Type and P447R Mutant Tryptophan Hydroxylase 2.Bulletin of experimental biology and medicine · 2025Article
- C-reactive protein: the nexus between inflammation and protein misfolding diseases.Frontiers in immunology · 2025Review
- Small-molecule correctors divert CFTR-F508del from ERAD by stabilizing sequential folding states.Molecular biology of the cell · 2024Article
- Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies.Frontiers in pharmacology · 2024Review
- Classical Hereditary galactosemia: findings in patients and animal models.Metabolic brain disease · 2024Review
- Deubiquitinase USP19 enhances phenylalanine hydroxylase protein stability and its enzymatic activity.Cell biology and toxicology · 2023Article
- Pharmacological Chaperones and Protein Conformational Diseases: Approaches of Computational Structural Biology.International journal of molecular sciences · 2023Review
- Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H.Molecular brain · 2022Article
- Quantifying lysosomal glycosidase activity within cells using bis-acetal substrates.Nature chemical biology · 2022Article
- Chemical Chaperones Modulate the Formation of Metabolite Assemblies.International journal of molecular sciences · 2021Article
- Dissection of pleiotropic effects of variants in and adjacent to F8 exon 19 and rescue of mRNA splicing and protein function.American journal of human genetics · 2021Article
- Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease.International journal of molecular sciences · 2021Review
- Modulation of Human Phenylalanine Hydroxylase by 3-Hydroxyquinolin-2(1H)-One Derivatives.Biomolecules · 2021Article
- Galactosemia: Towards Pharmacological Chaperones.Journal of personalized medicine · 2021Review
- Current and Future Treatments for Classic Galactosemia.Journal of personalized medicine · 2021Review
- Functional Recovery of a GCDH Variant Associated to Severe Deflavinylation-Molecular Insights into Potential Beneficial Effects of Riboflavin Supplementation in Glutaric Aciduria-Type I Patients.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To attain functionality, proteins must fold into their three-dimensional native state. The intracellular balance between protein synthesis, folding, and degradation is constantly challenged by genetic or environmental stress factors. In the last ten years, protein misfolding induced by missense mutations was demonstrated to be the seminal molecular mechanism in a constantly growing number of inborn errors of metabolism. In these cases, loss of protein function results from early degradation of missense-induced misfolded proteins. Increasing knowledge on the proteostasis network and the protein quality control system with distinct mechanisms in different compartments of the cell paved the way for the development of new treatment strategies for conformational diseases using small molecules. These comprise proteostasis regulators that enhance the capacity of the proteostasis network and pharmacological chaperones that specifically bind and rescue misfolded proteins by conformational stabilization. They can be used either alone or in combination, the latter to exploit synergistic effects. Many of these small molecule compounds currently undergo preclinical and clinical pharmaceutical development and two have been approved: saproterin dihydrochloride for the treatment of phenylketonuria and tafamidis for the treatment of transthyretin-related hereditary amyloidosis. Different technologies are exploited for the discovery of new small molecule compounds that belong to the still young class of pharmaceutical products discussed here. These compounds may in the near future improve existing treatment strategies or even offer a first-time treatment to patients suffering from nowadays-untreatable inborn errors of metabolism.
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