ArticleScientific reports2017
Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- The effects of microbiota abundance on symptom severity in Parkinson's disease: A systematic review.Frontiers in aging neuroscience · 2022Pooled it
- Design and Characterization of Bovine Serum Albumin Hydrogels: A Promising Platform for Controlled Drug Delivery.ACS omega · 2026Article
- Expanding the DAD9-Pegasus Scaffold: Synthesis and Functional Evaluation of Sulfur-Containing Dopamine-Tetracycline Conjugates for Parkinson's Disease.ChemMedChem · 2026Article
- 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
- Doxycycline: An essential tool for Alzheimer's disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ.NPJ Parkinson's disease · 2025Article
- Review
- Article
- Future is now: an Australasian perspective on disease-modifying trials in Parkinson's and prodromal disease.BMJ neurology open · 2025Article
- Microbiome-based therapeutics for Parkinson's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Antimicrobial and Hemostatic Diatom Biosilica Composite Sponge.Antibiotics (Basel, Switzerland) · 2024Article
- Doxycycline inhibits dopaminergic neurodegeneration through upregulation of axonal and synaptic proteins.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment.Journal of advanced research · 2023Review
- Simultaneous Determination of the Size and Shape of Single α-Synuclein Oligomers in Solution.ACS nano · 2023Article
- Doxycycline to treat levodopa-induced dyskinesias in Parkinson's disease: a preliminary study.Arquivos de neuro-psiquiatria · 2023Article
- Alpha Synuclein: Neurodegeneration and Inflammation.International journal of molecular sciences · 2023Review
- Neurodegeneration, Mitochondria, and Antibiotics.Metabolites · 2023Review
- Rescue of Dopamine Neurons from Iron-Dependent Ferroptosis by Doxycycline and Demeclocycline and Their Non-Antibiotic Derivatives.Antioxidants (Basel, Switzerland) · 2023Article
- The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment.International journal of molecular sciences · 2022Review
- Axon Guidance Molecules and Pain.Cells · 2022Review
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes α-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different β-sheet structural arrangement. These structural changes affect the α-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug.
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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.