ArticleHuman molecular genetics2014
Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Enamel Structure Defects inBiomedicines · 2023Article
- Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs.Scientific reports · 2022Article
- Phenylbutyrate modulates polyamine acetylase and ameliorates Snyder-Robinson syndrome in a Drosophila model and patient cells.JCI insight · 2022Article
- Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts.International journal of molecular sciences · 2022Article
- Facilitation of Reparative Dentin Using a Drug Repositioning Approach With 4-Phenylbutric Acid.Frontiers in physiology · 2022Article
- The effects of 4-Phenylbutyric acid on ER stress during mouse tooth development.Frontiers in physiology · 2022Article
- MMP20-generated amelogenin cleavage products prevent formation of fan-shaped enamel malformations.Scientific reports · 2021Article
- Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice.Frontiers in physiology · 2021Article
- Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta.Journal of dental research · 2019Article
- Canine models of human amelogenesis imperfecta: identification of novel recessive ENAM and ACP4 variants.Human genetics · 2019Article
- Gene cloning to clinical trials-the trials and tribulations of a life with collagen.International journal of experimental pathology · 2019Review
- Altered CaBiochimica et biophysica acta. Molecular cell research · 2018Review
- Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.Human molecular genetics · 2017Article
- The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.Frontiers in physiology · 2017Review
- Amelogenesis Imperfecta; Genes, Proteins, and Pathways.Frontiers in physiology · 2017Review
- Preparative SDS PAGE as an Alternative to His-Tag Purification of Recombinant Amelogenin.Frontiers in physiology · 2017Article
- 4-phenylbutyrate Mitigates Fluoride-Induced Cytotoxicity in ALC Cells.Frontiers in physiology · 2017Article
- Enamel Research: Priorities and Future Directions.Frontiers in physiology · 2017Article
- Integrative Temporo-Spatial, Mineralogic, Spectroscopic, and Proteomic Analysis of Postnatal Enamel Development in Teeth with Limited Growth.Frontiers in physiology · 2017Article
- Intravesicular Phosphatase PHOSPHO1 Function in Enamel Mineralization and Prism Formation.Frontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.
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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.