ArticleThe Journal of biological chemistry2011
Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils.
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. It is linked to trial NCT01677286 (A Phase II Study of Doxycycline in Patients With Amyloidosis), which is not on this map. Cited by 45 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.
A Phase II Study of Doxycycline in Patients With Amyloidosis
Who cites it
45 citing papers in PubMed, 104 citations in OpenAlex.
- Cellular prion protein and its derived peptides: multifaceted roles in neurodegenerative diseases and potential as biomarkers.Cell & bioscience · 2026Review
- DDOX expands the repertoire of tetracyclines for Parkinson's disease by preventing the cellular uptake and intracellular impact of α-synuclein preformed fibrils.Scientific reports · 2025Article
- High-Throughput Screening of Amyloid Inhibitors via Covalent-Labeling Mass Spectrometry.Analytical chemistry · 2025Article
- Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics-Part A: Endogenous Compounds and Repurposed Drugs.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Structure of cytotoxic amyloid oligomers generated during disaggregation.Journal of biochemistry · 2024Review
- Peritoneal Amyloid as a Presenting Manifestation of AL Amyloid.Journal of community hospital internal medicine perspectives · 2023Article
- Amyloid fibrils degradation: the pathway to recovery or aggravation of the disease?Frontiers in molecular biosciences · 2023Article
- Amyloid Disassembly: What Can We Learn from Chaperones?Biomedicines · 2022Review
- Catechol-containing compounds are a broad class of protein aggregation inhibitors: Redox state is a key determinant of the inhibitory activities.Pharmacological research · 2022Article
- Article
- Challenges of repurposing tetracyclines for the treatment of Alzheimer's and Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Mitochondria and Antibiotics: For Good or for Evil?Biomolecules · 2021Review
- Barriers to Small Molecule Drug Discovery for Systemic Amyloidosis.Molecules (Basel, Switzerland) · 2021Article
- Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates.Scientific reports · 2021Article
- CMT-3 targets different α-synuclein aggregates mitigating their toxic and inflammogenic effects.Scientific reports · 2020Article
- Insights into a Protein-Nanoparticle System by Paramagnetic Perturbation NMR Spectroscopy.Molecules (Basel, Switzerland) · 2020Article
- Structural Heterogeneity in the Preamyloid Oligomers of β-2-Microglobulin.Journal of molecular biology · 2020Article
- C. elegans expressing D76N βScientific reports · 2019Article
- The Anti-Amyloidogenic Action of Doxycycline: A Molecular Dynamics Study on the Interaction with Aβ42.International journal of molecular sciences · 2019Article
- Positron Emission Tomography Can Support the Diagnosis of Dialysis-Related Amyloidosis.Journal of clinical medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery of methods suitable for the conversion in vitro of native proteins into amyloid fibrils has shed light on the molecular basis of amyloidosis and has provided fundamental tools for drug discovery. We have studied the capacity of a small library of tetracycline analogues to modulate the formation or destructuration of β2-microglobulin fibrils. The inhibition of fibrillogenesis of the wild type protein was first established in the presence of 20% trifluoroethanol and confirmed under a more physiologic environment including heparin and collagen. The latter conditions were also used to study the highly amyloidogenic variant, P32G. The NMR analysis showed that doxycycline inhibits β2-microglobulin self-association and stabilizes the native-like species through fast exchange interactions involving specific regions of the protein. Cell viability assays demonstrated that the drug abolishes the natural cytotoxic activity of soluble β2-microglobulin, further strengthening a possible in vivo therapeutic exploitation of this drug. Doxycycline can disassemble preformed fibrils, but the IC(50) is 5-fold higher than that necessary for the inhibition of fibrillogenesis. Fibril destructuration is a dynamic and time-dependent process characterized by the early formation of cytotoxic protein aggregates that, in a few hours, convert into non-toxic insoluble material. The efficacy of doxycycline as a drug against dialysis-related amyloidosis would benefit from the ability of the drug to accumulate just in the skeletal system where amyloid is formed. In these tissues, the doxycycline concentration reaches values several folds higher than those resulting in inhibition of amyloidogenesis and amyloid destructuration in vitro.
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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.