ArticleProceedings of the National Academy of Sciences of the United States of America2011
Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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122 citing papers in PubMed, 194 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Mito-TEMPO improves survival rates inScience advances · 2026Article
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- Epidrug screening identifies type I PRMT inhibitors as modulators of lysosomal exocytosis and drug sensitivity in cancers.Cell death & disease · 2025Article
- Exploration of Bromodomain Proteins as Drug Targets for Niemann-Pick Type C Disease.International journal of molecular sciences · 2025Article
- 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
- Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.JCI insight · 2024Article
- Sterol O-Acyltransferase 1 (International journal of molecular sciences · 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
- Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.Frontiers in pharmacology · 2024Review
- Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine.NPJ genomic medicine · 2023Review
- Lithium ameliorates Niemann-Pick C1 disease phenotypes by impeding STING/SREBP2 activation.iScience · 2023Article
- Investigation of 2-Hydroxypropyl-β-Cyclodextrin Treatment in a Neuronal-Like Cell Model of Niemann-Pick Type C Using Quantitative Proteomics.Journal of the American Society for Mass Spectrometry · 2023Article
- The landscape of CRISPR/Cas9 for inborn errors of metabolism.Molecular genetics and metabolism · 2023Review
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- Mass spectrometry-based proteomics in neurodegenerative lysosomal storage disorders.Molecular omics · 2022Review
- Upregulation of SNAP25 by HDAC inhibition ameliorates Niemann-Pick Type C disease phenotypes via autophagy induction.Clinical and translational medicine · 2022Article
- Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes.Nature communications · 2022Article
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62 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
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Abstract
Niemann-Pick type C (NPC) disease is predominantly caused by mutations in the NPC1 protein that affect intracellular cholesterol trafficking and cause accumulation of unesterified cholesterol and other lipids in lysosomal storage organelles. We report the use of a series of small molecule histone deacetylase (HDAC) inhibitors in tissue culture models of NPC human fibroblasts. Some HDAC inhibitors lead to a dramatic correction in the NPC phenotype in cells with either one or two copies of the NPC1(I1061T) mutation, and for several of the inhibitors, correction is associated with increased expression of NPC1 protein. Increased NPC1(I1061T) protein levels may partially account for the correction of the phenotype, because this mutant can promote cholesterol efflux if it is delivered to late endosomes and lysosomes. The HDAC inhibitor treatment is ineffective in an NPC2 mutant human fibroblast line. Analysis of the isoform selectivity of the compounds used implicates HDAC1 and/or HDAC2 as likely targets for the observed correction, although other HDACs may also play a role. LBH589 (panobinostat) is an orally available HDAC inhibitor that crosses the blood-brain barrier and is currently in phase III clinical trials for several types of cancer. It restores cholesterol homeostasis in cultured NPC1 mutant fibroblasts to almost normal levels within 72 h when used at 40 nM. The findings that HDAC inhibitors can correct cholesterol storage defects in human NPC1 mutant cells provide the potential basis for treatment options for NPC disease.
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