ReviewCurrent pharmaceutical design2014
Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" - from the test tube to animal models.
Review in Current pharmaceutical design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Anti-amyloid treatment is broadly effective in neuronopathic mucopolysaccharidoses and synergizes with gene therapy in MPS-IIIA.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Three-repeat and four-repeat tau isoforms form different oligomers.Protein science : a publication of the Protein Society · 2022Article
- Inhibition of Staphylococcus aureus biofilm-forming functional amyloid by molecular tweezers.Cell chemical biology · 2021Article
- Lysine-selective molecular tweezers are cell penetrant and concentrate in lysosomes.Communications biology · 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
- Capture carcinogenic aromatic compounds by the design of new tweezer compounds: a theoretical study.Journal of molecular modeling · 2020Article
- Different Inhibitors of Aβ42-Induced Toxicity Have Distinct Metal-Ion Dependency.ACS chemical neuroscience · 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
- Protein Aggregation and Dysfunction of Autophagy-Lysosomal Pathway: A Vicious Cycle in Lysosomal Storage Diseases.Frontiers in molecular neuroscience · 2020Article
- The molecular tweezer CLR01 reduces aggregated, pathologic, and seeding-competent α-synuclein in experimental multiple system atrophy.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Major Differences between the Self-Assembly and Seeding Behavior of Heparin-Induced and in Vitro Phosphorylated Tau and Their Modulation by Potential Inhibitors.ACS chemical biology · 2019Article
- The molecular tweezer CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assemblyThe Journal of biological chemistry · 2019Article
- Native Top-Down Mass Spectrometry and Ion Mobility Spectrometry of the Interaction of Tau Protein with a Molecular Tweezer Assembly Modulator.Journal of the American Society for Mass Spectrometry · 2019Article
- Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins.Methods in molecular biology (Clifton, N.J.) · 2018Article
- New Perspectives on Roles of Alpha-Synuclein in Parkinson's Disease.Frontiers in aging neuroscience · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Despite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful disease-modifying drugs for amyloidoses stems from the nature of the targets for such drugs - primarily oligomers of amyloidogenic proteins, which are distinct from traditional targets, such as enzymes or receptors. The oligomers are metastable, do not have well-defined structures, and exist in dynamically changing mixtures. Therefore, inhibiting the formation and toxicity of these oligomers likely will require out-of-the-box thinking and novel strategies. We review here the development of a strategy based on targeting the combination of hydrophobic and electrostatic interactions that are key to the assembly and toxicity of amyloidogenic proteins using lysine (K)-specific "molecular tweezers" (MTs). Our discussion includes a survey of the literature demonstrating the important role of K residues in the assembly and toxicity of amyloidogenic proteins and the development of a lead MT derivative called CLR01, from an inhibitor of protein aggregation in vitro to a drug candidate showing effective amelioration of disease symptoms in animal models of Alzheimer's and Parkinson's diseases.
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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.