ArticleThe Biochemical journal2020
Proteostasis regulators modulate proteasomal activity and gene expression to attenuate multiple phenotypes in Fabry disease.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG).International journal of molecular sciences · 2022Pooled it
- Pathophysiological mechanisms of organ injury in Fabry disease: Update via multi-omics.Genes & diseases · 2026Review
- Bioinformatics-Driven Multi-Factorial Insight into α-Galactosidase Mutations.International journal of molecular sciences · 2025Article
- Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification.Biomolecules · 2023Review
- Long-Term Monitoring of Cardiac Involvement under Migalastat Treatment Using Magnetic Resonance Tomography in Fabry Disease.Life (Basel, Switzerland) · 2023Article
- Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy.International journal of molecular sciences · 2023Article
- How to fix a broken protein: restoring function to mutant human cystathionine β-synthase.Human genetics · 2022Review
- Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones.International journal of molecular sciences · 2022Article
- Mechanistic Insight into the Mode of Action of Acid β-Glucosidase Enhancer Ambroxol.International journal of molecular sciences · 2022Article
- Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease.International journal of molecular sciences · 2021Review
- The rapidly evolving view of lysosomal storage diseases.EMBO molecular 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
- Misfolding of Lysosomal α-Galactosidase a in a Fly Model and Its Alleviation by the Pharmacological Chaperone Migalastat.International journal of molecular sciences · 2020Article
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- Lysosomal storage diseases in North America: a comprehensive review of enzyme therapies and unmet needs.Therapeutic advances in rare diseaseReview
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lysosomal storage disorder Fabry disease is characterized by a deficiency of the lysosomal enzyme α-Galactosidase A. The observation that missense variants in the encoding GLA gene often lead to structural destabilization, endoplasmic reticulum retention and proteasomal degradation of the misfolded, but otherwise catalytically functional enzyme has resulted in the exploration of alternative therapeutic approaches. In this context, we have investigated proteostasis regulators (PRs) for their potential to increase cellular enzyme activity, and to reduce the disease-specific accumulation of the biomarker globotriaosylsphingosine in patient-derived cell culture. The PRs also acted synergistically with the clinically approved 1-deoxygalactonojirimycine, demonstrating the potential of combination treatment in a therapeutic application. Extensive characterization of the effective PRs revealed inhibition of the proteasome and elevation of GLA gene expression as paramount effects. Further analysis of transcriptional patterns of the PRs exposed a variety of genes involved in proteostasis as potential modulators. We propose that addressing proteostasis is an effective approach to discover new therapeutic targets for diseases involving folding and trafficking-deficient protein mutants.
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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.