Ceftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro
Open accessAbstract
The β-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in several neurodegenerative disorders, either for its ability to counteract glutamate-mediated toxicity, as in cerebral ischemia, or for its ability to enhance the degradation of misfolded proteins, as in Alexander's disease. Recently, the efficacy of ceftriaxone in neuroprotection of dopaminergic neurons in a rat model of Parkinson's disease was documented. However, which characteristics of ceftriaxone mediate its therapeutic effects remains unclear. Since, at the molecular level, neuronal α-synuclein inclusions and pathological α-synuclein transmission play a leading role in initiation of Parkinson-like neurodegeneration, we thought of investigating, by circular dichroism spectroscopy, the capability of ceftriaxone to interact with α-synuclein. We found that ceftriaxone binds with good affinity to α-synuclein and blocks its in vitro polymerization. Considering this finding, we also documented that ceftriaxone exerts neuroprotective action in an in vitro model of Parkinson's disease. Our data, in addition to the findings on neuroprotective activity of ceftriaxone on Parkinson-like neurodegeneration in vivo, indicates ceftriaxone as a potential agent in treatment of Parkinson's disease.
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CTX binds to α-synuclein with considerable affinity in vitro.
“Moreover, it has been observed that CTX binds to α-synuclein with considerable affinity and prevents its polymerization in vitro [226,230,231].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [230]
CTX prevents α-synuclein polymerization in vitro.
“Moreover, it has been observed that CTX binds to α-synuclein with considerable affinity and prevents its polymerization in vitro [226,230,231].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [230]
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- Authors
- Ruzza, P., Siligardi, G., Hussain, R., Marchiani, A., Islami, M., Bubacco, L., Delogu, G., Fabbri, D., Dettori, M. A., Sechi, M., Pala, N., Spissu, Y., Migheli, R., Serra, P. A., & Sechi, G.
- Affiliations
- National Research Council (IT)
- Diamond Light Source (GB)
- University of Padua (IT)
- University of Sassari (IT)
- Corresponding author
- Ruzza, Paolo
- Sechi, GianPietro
- ORCID
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-10-07
- Volume
- 5
- Issue
- 1
- Pages
- 30-38
- ISSN
- 1948-7193 (ISSN-L)
- PMC
- PMC3894726
- OpenAlex
- W2035131474
- Cited by
- 70
- References
- 39
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 3
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- ceftriaxone, alpha-synuclein, protein polymerization, neuroprotection, Parkinson's disease, beta-lactam antibiotics, protein-protein binding, dopaminergic neurons, neurodegeneration, circular dichroism
- MeSH terms
- Animals, Ceftriaxone, Computer Simulation, Dose-Response Relationship, Drug, Flow Cytometry, Kinetics, Models, Molecular, Protein Binding, Mass Spectrometry, Time Factors, Oxidopamine, PC12 Cells, Adrenergic Agents, Neuroprotective Agents, Rats, alpha-Synuclein, Polymerization
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