S100B protein as a therapeutic target in multiple sclerosis: The S100B inhibitor arundic acid protects from chronic experimental autoimmune encephalomyelitis

Francesco Ria, Maria Elisabetta Clementi, Maria Tredicine, Fabrizio Michetti, Gabriele Di Sante, Susanna Amadio, Beatrice Sampaolese, Cinzia Volonté, Vincenzo Romano Spica, Rosa Di Liddo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.
Lingua originaleEnglish
pagine (da-a)13558-N/A
RivistaInternational Journal of Molecular Sciences
Volume22
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • Animals
  • Arundic acid
  • Caprylates
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental
  • Experimental autoimmune encephalomyelitis
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Multiple Sclerosis
  • Multiple sclerosis
  • S100 Calcium Binding Protein beta Subunit
  • S100B inhibitor

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