ReviewCurrent topics in medicinal chemistry2012
Phenylalanine hydroxylase misfolding and pharmacological chaperones.
Review in Current topics in medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 63 citations in OpenAlex.
- Optimising Formulations for Paediatric Patients with Inherited Metabolic Disorders: The Case Study of Levocarnitine.Pharmaceutical medicine · 2026Review
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- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Aromatic Amino Acid Hydroxylases as Off-Targets of Histone Deacetylase Inhibitors.ACS chemical neuroscience · 2024Article
- A Phase 1 Study to Assess the Pharmacokinetics, Food Effect, Safety, and Tolerability of Sepiapterin in Healthy Japanese and Non-Japanese Participants.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Longitudinal Dietary Intake Data in Patients with Phenylketonuria from Europe: The Impact of Age and Phenylketonuria Severity.Nutrients · 2024Article
- Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.Nature communications · 2022Article
- Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia-A Focus on Tyrosine Hydroxylase Deficiency.Journal of personalized medicine · 2021Review
- Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators.International journal of molecular sciences · 2021Review
- Engineering Organoids forFrontiers in molecular neuroscience · 2021Review
- Protein Degradation and the Pathologic Basis of Phenylketonuria and Hereditary Tyrosinemia.International journal of molecular sciences · 2020Review
- Second-Generation Pharmacological Chaperones: Beyond Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- A Pharmacological Chaperone Therapy for Acute Intermittent Porphyria.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- EU-OPENSCREEN: A Novel Collaborative Approach to Facilitate Chemical Biology.SLAS discovery : advancing life sciences R & D · 2019Article
- The quaternary structure of human tyrosine hydroxylase: effects of dystonia-associated missense variants on oligomeric state and enzyme activity.Journal of neurochemistry · 2019Article
- Generation of urine-derived induced pluripotent stem cells from a patient with phenylketonuria.Intractable & rare diseases research · 2018Article
- Conformational stabilization as a strategy to prevent nucleophosmin mislocalization in leukemia.Scientific reports · 2017Article
- Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain.Scientific reports · 2016Article
- A commentary on the utility of a new L-DOPA-responsive dystonia mouse model.Rare diseases (Austin, Tex.) · 2016Article
- Innovative strategies to treat protein misfolding in inborn errors of metabolism: pharmacological chaperones and proteostasis regulators.Journal of inherited metabolic disease · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU) is a loss-of-function inborn error of metabolism. As many other inherited diseases the main pathologic mechanism in PKU is an enhanced tendency of the mutant phenylalanine hydroxylase (PAH) to misfold and undergo ubiquitin-dependent degradation. Recent alternative approaches with therapeutic potential for PKU aim at correcting the PAH misfolding, and in this respect pharmacological chaperones are the focus of increasing interest. These compounds, which often resemble the natural ligands and show mild competitive inhibition, can rescue the misfolded proteins by stimulating their renaturation in vivo. For PKU, a few studies have proven the stabilization of PKU-mutants in vitro, in cells, and in mice by pharmacological chaperones, which have been found either by using the tetrahydrobiopterin (BH(4)) cofactor as query structure for shape-focused virtual screening or by high-throughput screening of small compound libraries. Both approaches have revealed a number of compounds, most of which bind at the iron-binding site, competitively with respect to BH(4). Furthermore, PAH shares a number of ligands, such as BH(4), amino acid substrates and inhibitors, with the other aromatic amino acid hydroxylases: the neuronal/neuroendocrine enzymes tyrosine hydroxylase (TH) and the tryptophan hydroxylases (TPHs). Recent results indicate that the PAH-targeted pharmacological chaperones should also be tested on TH and the TPHs, and eventually be derivatized to avoid unwanted interactions with these other enzymes. After derivatization and validation in animal models, the PAH-chaperoning compounds represent novel possibilities in the treatment of PKU.
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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.