ArticleJournal of endocrinological investigation2020
Effect of 4-phenylbutyrate and valproate on dominant mutations of WFS1 gene in Wolfram syndrome.
Article in Journal of endocrinological investigation, 2020. 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, 19 citations in OpenAlex.
- Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum.International journal of environmental research and public health · 2022Pooled it
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.Journal of biomedical science · 2024Review
- Article
- Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.International journal of molecular sciences · 2023Review
- Disruption of the Ubiquitin-Proteasome System and Elevated Endoplasmic Reticulum Stress in Epilepsy.Biomedicines · 2022Review
- Metabolic Treatment of Wolfram Syndrome.International journal of environmental research and public health · 2022Review
- Functional analysis ofClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2022Article
- The Expression of RAAS Key Receptors,Genes · 2021Article
- A novel mutation of WFS1 gene leading to increase ER stress and cell apoptosis is associated an autosomal dominant form of Wolfram syndrome type 1.BMC endocrine disorders · 2021Article
- Collaboration for rare diabetes: understanding new treatment options for Wolfram syndrome.Endocrine · 2021Review
- Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders.Frontiers in pharmacology · 2021Review
- Wolfram Syndrome: a Monogenic Model to Study Diabetes Mellitus and Neurodegeneration.Current opinion in physiology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWolfram syndrome (WS) is a rare disorder caused by mutations in WFS1 that is characterized by diabetes mellitus, optic atrophy, sensorineural deafness, diabetes insipidus, and neurodegeneration. This disease is usually inherited as an autosomal recessive trait, but an autosomal dominant form has been reported. WFS1 encodes a transmembrane protein, which is a maintenance component of endoplasmic homeostasis. These dominant mutations were thought to increase endoplasmic reticulum (ER) stress. Recent studies suggest that 4-phenylbutyrate (PBA) and valproate (VPA) reduce ER stress. The objective of this study was to analyze the effect of PBA and VPA on dominant WFS1 mutants in vitro.
methodsWe determined whether dominant WFS1 mutants (p.His313Tyr, p.Trp314Arg, p.Asp325_Ile328del, p.Glu809Lys, and p.Glu864Lys) have the dominant negative effect using a luciferase assay of ER stress response element marker as ER stress. Moreover, the rescue of cell apoptosis induced by dominant WFS1 mutants following treatment with PBA or VPA was determined by quantitative real-time PCR of C/EBP homologous protein (CHOP) mRNA expression.
resultsThese mutants showed the dominant negative effect on the wild-type WFS1. In addition, the levels of ER stress and CHOP mRNA were significantly elevated by all dominant WFS1 mutants. After treatment with PBA or VPA, ER stress and cell apoptosis were reduced in each mutant.
conclusionsPBA and VPA could reduce the ER stress and cell apoptosis caused by dominant WFS1 mutants.
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