Oxidative Modifications of Cerebral Transthyretin are Associated with Multiple Sclerosis

Transthyretin (TTR) is an homotetrameric protein of the Central Nervous System (CNS) that plays the role of 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 (MS) 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 MS patients, suggestive of a potential role of these modifications on T4 transport into the brain.