ArticleMolecular pharmaceutics2014
Clathrin-mediated endocytosis is impaired in type A-B Niemann-Pick disease model cells and can be restored by ICAM-1-mediated enzyme replacement.
Article in Molecular pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Article
- Effect of acid sphingomyelinase deficiency in type A Niemann-Pick disease on the transport of therapeutic nanocarriers across the blood-brain barrier.Drug delivery and translational research · 2023Article
- Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.International journal of molecular sciences · 2023Article
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Article
- Taming the Triskelion: Bacterial Manipulation of Clathrin.Microbiology and molecular biology reviews : MMBR · 2019Review
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- A Comparative Study on the Alterations of Endocytic Pathways in Multiple Lysosomal Storage Disorders.Molecular pharmaceutics · 2016Article
- Altered Clathrin-Independent Endocytosis in Type A Niemann-Pick Disease Cells and Rescue by ICAM-1-Targeted Enzyme Delivery.Molecular pharmaceutics · 2015Article
- Targeting, endocytosis, and lysosomal delivery of active enzymes to model human neurons by ICAM-1-targeted nanocarriers.Pharmaceutical research · 2015Article
- ICAM-1 targeting, intracellular trafficking, and functional activity of polymer nanocarriers coated with a fibrinogen-derived peptide for lysosomal enzyme replacement.Journal of drug targetingArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Drugs often use endocytosis to achieve intracellular delivery, either by passive uptake from the extracellular fluid or by active targeting of cell surface features such as endocytic receptors. An example is enzyme replacement therapy, a clinically practiced treatment for several lysosomal storage diseases where glycosylated recombinant enzymes naturally target the mannose-6-phosphate receptor and are internalized by clathrin mediated endocytosis (CME). However, lysosomal substrate accumulation, a hallmark of these diseases, has been indirectly linked to aberrant endocytic activity. These effects are poorly understood, creating an obstacle to therapeutic efficiency. Here we explored endocytic activity in fibroblasts from patients with type A Niemann-Pick disease, a lysosomal storage disease characterized by acid sphingomyelinase (ASM) deficiency. The uptake of fluid phase markers and clathrin-associated ligands, formation of endocytic structures, and recruitment of intracellular clathrin to ligand binding sites were all altered, demonstrating aberrant CME in these cells. Model polymer nanocarriers targeted to intercellular adhesion molecule-1 (ICAM-1), which are internalized by a clathrin-independent route, enhanced the intracellular delivery of recombinant ASM more than 10-fold compared to free enzyme. This strategy reduced substrate accumulation and restored clathrin endocytic activity to wild-type levels. There appears to be a relationship between lysosomal storage and diminished CME, and bypassing this pathway by targeting ICAM-1 may enhance future therapies for lysosomal storage diseases.
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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.