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.
Highlights
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss
S100B is a small EF-related Ca2+ and Zn2+ -binding protein, which is mainly synthesized by astrocytes in the nervous system and, to a lesser extent, by oligodendrocytes
GFAP+ ) and demyelination on C1–C4 cervical spinal cord segments, where neuropathological biomarkers are known to be especially apparent in this MS animal model, comparing EAE mice treated with the vehicle or arundic acid (AA)
Summary
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss. S100B is a small EF-related Ca2+ and Zn2+ -binding protein (a helix−loop−helix structure is formed by the E and F helices), which is mainly synthesized by astrocytes in the nervous system and, to a lesser extent, by oligodendrocytes It exerts both intracellular and extracellular actions. We have demonstrated that pentamidine (PTM), an approved antiprotozoal drug known to block S100B activity [11,12], ameliorates clinical disease scores and neuropathologic and biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis SJL/J mouse model of MS [13]. This suggests that S100B neutralization emerges as a promising therapeutic target in MS. People affected by this form of MS can only benefit from symptomatic therapy [16,17]
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