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Ceftriaxone blocks the polymerization of α-synuclein and exerts neuroprotective effects in vitro

Ruzza, Paolo and Siligardi, Giuliano and Hussain, Rohanah and Marchiani, Anna and Islami, Mehmet and Bubacco, Luigi and Delogu, Giovanna and Fabbri, Davide and Dettori, Maria Antonietta and Sechi, Mario and Pala, Nicolino and Spissu, Ylenia and Migheli, Rossana and Serra, Pier Andrea and Sechi, Gianpietro (2014) Ceftriaxone blocks the polymerization of α-synuclein and exerts neuroprotective effects in vitro. ACS Chemical neuroscience, Vol. 5 (1), p. 30-38. eISSN 1948-7193. Article.

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DOI: 10.1021/cn400149k

Abstract

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.

Item Type:Article
ID Code:9915
Status:Published
Refereed:Yes
Uncontrolled Keywords:Ceftriaxone, α-synuclein, Parkinson’s disease, circular dichroism, 6-OHDA, PC12 cells
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
Area 06 - Scienze mediche > MED/26 Neurologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:American Chemical Society
eISSN:1948-7193
Deposited On:25 Jun 2014 10:14

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