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Oxidative modifications of cerebral transthyretin are associated with multiple sclerosis

Authors

  • Damiana Pieragostino,

    Corresponding author
    1. Department of Experimental and Clinical Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
    • Research Centre on Aging (Ce.S.I), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Piero Del Boccio,

    1. Research Centre on Aging (Ce.S.I), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
    2. Department of Experimental and Clinical Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Maria Di Ioia,

    1. Department of Neurosciences and Imaging, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Luisa Pieroni,

    1. IRCCS-Santa Lucia Foundation, Rome, Italy
    2. Department of Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy
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  • Viviana Greco,

    1. IRCCS-Santa Lucia Foundation, Rome, Italy
    2. Department of Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy
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  • Giovanna De Luca,

    1. Department of Neurosciences and Imaging, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Simona D'Aguanno,

    1. IRCCS-Santa Lucia Foundation, Rome, Italy
    2. Department of Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy
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  • Claudia Rossi,

    1. Research Centre on Aging (Ce.S.I), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
    2. Department of Experimental and Clinical Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Diego Franciotta,

    1. Laboratory of Neuroimmunology (IRCCS) National Neurological Institute C. Mondino, Pavia, Italy
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  • Diego Centonze,

    1. IRCCS-Santa Lucia Foundation, Rome, Italy
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  • Paolo Sacchetta,

    1. Research Centre on Aging (Ce.S.I), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
    2. Department of Experimental and Clinical Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Carmine Di Ilio,

    1. Research Centre on Aging (Ce.S.I), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
    2. Department of Experimental and Clinical Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Alessandra Lugaresi,

    1. Department of Neurosciences and Imaging, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
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  • Andrea Urbani

    1. IRCCS-Santa Lucia Foundation, Rome, Italy
    2. Department of Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy
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  • Colour Online: See the article online to view Figs. and in colour.

Correspondence: Dr. Damiana Pieragostino, Department of Experimental and Clinical Sciences, University “G. d'Annunzio,” Chieti-Pescara, Italy

E-mail: dpieragostino@unich.it

Fax: +39-0871-541598

Abstract

Transthyretin (TTR) is a homotetrameric protein of the CNS that plays a role of as the major thyroxine (T4) carrier from blood to cerebrospinal fluid (CSF). T4 physiologically helps oligodendrocyte precursor cells to turn into myelinating oligodendrocytes, enhancing remyelination after myelin sheet damage. We investigated post-translational oxidative modifications of serum and CSF TTR in multiple sclerosis subjects, highlighting high levels of S-sulfhydration and S-sulfonation of cysteine in position ten only in the cerebral TTR, which correlate with an anomalous TTR protein folding as well as with disease duration. Moreover, we found low levels of free T4 in CSF of multiple sclerosis patients, suggestive of a potential role of these modifications in T4 transport into the brain.

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