ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2014
Molecular tweezers targeting transthyretin amyloidosis.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- In vitro and in vivo disease models of cardiac amyloidosis: progress, pitfalls, and potential.Cardiovascular research · 2025Review
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Development of Small Molecules Targeting α-Synuclein Aggregation: A Promising Strategy to Treat Parkinson's Disease.Pharmaceutics · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Cellular environment of TTR deposits in an animal model of ATTR-Cardiomyopathy.Frontiers in molecular biosciences · 2023Article
- Molecular Probes, Chemosensors, and Nanosensors for Optical Detection of Biorelevant Molecules and Ions in Aqueous Media and Biofluids.Chemical reviews · 2022Review
- Molecular Mechanisms of Cardiac Amyloidosis.International journal of molecular sciences · 2021Review
- Lysine-selective molecular tweezers are cell penetrant and concentrate in lysosomes.Communications biology · 2021Article
- The Molecular Tweezer CLR01 Inhibits Antibody-Resistant Cell-to-Cell Spread of Human Cytomegalovirus.Viruses · 2021Article
- The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice.Alzheimer's research & therapy · 2021Article
- Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers.Journal of the American Chemical Society · 2020Article
- The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Modulation of the Mechanisms Driving Transthyretin Amyloidosis.Frontiers in molecular neuroscience · 2020Review
- Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors.Drug design, development and therapy · 2020Review
- Tegsedi (Inotersen): An Antisense Oligonucleotide Approved for the Treatment of Adult Patients with Hereditary Transthyretin Amyloidosis.Pharmaceuticals (Basel, Switzerland) · 2019Article
- Pharmaceutical Applications of Molecular Tweezers, Clefts and Clips.Molecules (Basel, Switzerland) · 2019Review
- Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis.International journal of molecular sciences · 2019Review
- The molecular tweezer CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assemblyThe Journal of biological chemistry · 2019Article
- Contributions of Animal Models to the Mechanisms and Therapies of Transthyretin Amyloidosis.Frontiers in physiology · 2019Review
- The molecular tweezer CLR01 inhibits Ebola and Zika virus infection.Antiviral research · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Transthyretin (TTR) amyloidoses comprise a wide spectrum of acquired and hereditary diseases triggered by extracellular deposition of toxic TTR aggregates in various organs. Despite recent advances regarding the elucidation of the molecular mechanisms underlying TTR misfolding and pathogenic self-assembly, there is still no effective therapy for treatment of these fatal disorders. Recently, the "molecular tweezers", CLR01, has been reported to inhibit self-assembly and toxicity of different amyloidogenic proteins in vitro, including TTR, by interfering with hydrophobic and electrostatic interactions known to play an important role in the aggregation process. In addition, CLR01 showed therapeutic effects in animal models of Alzheimer's disease and Parkinson's disease. Here, we assessed the ability of CLR01 to modulate TTR misfolding and aggregation in cell culture and in an animal model. In cell culture assays we found that CLR01 inhibited TTR oligomerization in the conditioned medium and alleviated TTR-induced neurotoxicity by redirecting TTR aggregation into the formation of innocuous assemblies. To determine whether CLR01 was effective in vivo, we tested the compound in mice expressing TTR V30M, a model of familial amyloidotic polyneuropathy, which recapitulates the main pathological features of the human disease. Immunohistochemical and Western blot analyses showed a significant decrease in TTR burden in the gastrointestinal tract and the peripheral nervous system in mice treated with CLR01, with a concomitant reduction in aggregate-induced endoplasmic reticulum stress response, protein oxidation, and apoptosis. Taken together, our preclinical data suggest that CLR01 is a promising lead compound for development of innovative, disease-modifying therapy for TTR amyloidosis.
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Registered trials
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.