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

Autor: Camponeschi C; Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy., De Carluccio M; Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.; Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy., Amadio S; IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, Italy., Clementi ME; Istituto di Scienze e Tecnologie Chimiche 'Giulio Natta' SCITEC-CNR, Largo Francesco Vito 1, 00168 Rome, Italy., Sampaolese B; Istituto di Scienze e Tecnologie Chimiche 'Giulio Natta' SCITEC-CNR, Largo Francesco Vito 1, 00168 Rome, Italy., Volonté C; IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, Italy.; National Research Council, Institute for Systems Analysis and Computer Science, Via dei Taurini 19, 00185 Rome, Italy., Tredicine M; Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy., Romano Spica V; Department of Movement, Human and Health Sciences, Laboratory of Epidemiology and Biotechnologies, University of Rome 'Foro Italico', Piazza Lauro De Bosis 6, 00135 Rome, Italy., Di Liddo R; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo 5, 35131 Padua, Italy., Ria F; Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.; Department Laboratory and Infectious Diseases Sciences, Fondazione Policlinico Universitario, A. Gemelli IRCCS, Largo Agostino Gemelli 1-8, 00168 Rome, Italy., Michetti F; Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.; IRCCS San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, via Olgettin 60, 20121 Milan, Italy., Di Sante G; Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.; Department of Surgery and Medicine, Institute of Human, Clinical and Forensic Anatomy, Piazza L. Severi 1, 06125 Perugia, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Dec 17; Vol. 22 (24). Date of Electronic Publication: 2021 Dec 17.
DOI: 10.3390/ijms222413558
Abstrakt: 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.
Databáze: MEDLINE
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