The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing-Remitting Multiple Sclerosis Mouse Model

Gabriele Di Sante, Susanna Amadio, Beatrice Sampaolese, Maria Elisabetta Clementi, Mariagrazia Valentini, Cinzia Volonté, Patrizia Casalbore, Francesco Ria, Fabrizio Michetti

Research output: Contribution to journalArticlepeer-review

Abstract

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing-remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.

Original languageEnglish
JournalCells
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 18 2020

Keywords

  • multiple sclerosis
  • pentamidine
  • relapsing–remitting experimental autoimmune encephalomyelitis
  • S100B

ASJC Scopus subject areas

  • Medicine(all)

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