ArticleThe Journal of biological chemistry2011
Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 96 citations in OpenAlex.
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- Lethal toxin-equipped effector cells for the potential treatment of cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evaluation of the cellular impact of missense variants in low-density lipoprotein receptor-related protein 6 (LRP6) associated with cardiovascular diseases in HeLa and HEK293T cell lines.Frontiers in cell and developmental biology · 2026Article
- High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- StaufenC facilitates utilization of the ERAD pathway to transport dsRNA through the endoplasmic reticulum to the cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?Lipids in health and disease · 2024Article
- Development of quantitative high-throughput screening assays to identify, validate, and optimize small-molecule stabilizers of misfolded β-glucocerebrosidase with therapeutic potential for Gaucher disease and Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- Mechanistic Insights into Dibasic Iminosugars as pH-Selective Pharmacological Chaperones to Stabilize Human α-Galactosidase.JACS Au · 2024Article
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2.Cells · 2024Article
- Identification of genotype-biochemical phenotype correlations associated with fructose 1,6-bisphosphatase deficiency.Communications biology · 2023Article
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.Human molecular genetics · 2023Article
- Disrupting N-Glycosylation Using Type I Mannosidase Inhibitors Alters B-Cell Receptor Signaling.ACS pharmacology & translational science · 2022Article
- Review
- Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Protein kinase R is an innate immune sensor of proteotoxic stress via accumulation of cytoplasmic IL-24.Science immunology · 2022Article
- Pharmacological targeting of endoplasmic reticulum stress in disease.Nature reviews. Drug discovery · 2022Review
- Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington's Disease.International journal of molecular sciences · 2022Review
- Golgi Alpha1,2-Mannosidase IA Promotes Efficient Endoplasmic Reticulum-Associated Degradation of NKCC2.Cells · 2021Article
4 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomal storage disorders are often caused by mutations that destabilize native folding and impair trafficking of secretory proteins. We demonstrate that endoplasmic reticulum (ER)-associated degradation (ERAD) prevents native folding of mutated lysosomal enzymes in patient-derived fibroblasts from two clinically distinct lysosomal storage disorders, namely Gaucher and Tay-Sachs disease. Prolonging ER retention via ERAD inhibition enhanced folding, trafficking, and activity of these unstable enzyme variants. Furthermore, combining ERAD inhibition with enhancement of the cellular folding capacity via proteostasis modulation resulted in synergistic rescue of mutated enzymes. ERAD inhibition was achieved by cell treatment with small molecules that interfere with recognition (kifunensine) or retrotranslocation (eeyarestatin I) of misfolded substrates. These different mechanisms of ERAD inhibition were shown to enhance ER retention of mutated proteins but were associated with dramatically different levels of ER stress, unfolded protein response activation, and unfolded protein response-induced apoptosis.
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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.