S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis.

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.

• Authors: Chiara Camponeschi, Maria De Carluccio, Susanna Amadio, Maria Elisabetta Clementi, Beatrice Sampaolese, Cinzia Volonté, Maria Tredicine, Vincenzo Romano Spica, Rosa Di Liddo, Francesco Ria, Fabrizio Michetti, Gabriele Di Sante
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 24 (Dec 17 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34948360 (Publication Type: Journal Article)

Chemical References

• Caprylates
• ONO2506
• S100 Calcium Binding Protein beta Subunit
• S100b protein, mouse

Topics

• Animals
• Caprylates (pharmacology, therapeutic use)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, metabolism)
• Female
• Mice
• Mice, Inbred C57BL
• Molecular Targeted Therapy
• Multiple Sclerosis (drug therapy, metabolism)
• S100 Calcium Binding Protein beta Subunit (antagonists & inhibitors, metabolism)