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.
Int J Mol Sci. 2021 Dec 17;22(24):13558. doi: 10.3390/ijms222413558.
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.
S100B 是一种星形胶质细胞蛋白，在高浓度下表现为损伤相关分子模式分子。已经证明 S100B 含量的增加与炎症过程直接相关，特别是 S100B 活性抑制剂戊脒已被证明可改善多发性硬化症的复发缓解型实验性自身免疫性脑脊髓炎小鼠模型的临床评分和神经病理生物标志物参数。本研究调查了已知抑制星形胶质细胞 S100B 合成的阿仑酸（AA）在慢性实验性自身免疫性脑脊髓炎中的作用，这是另一种通常研究的多发性硬化症小鼠模型。通过对脊髓进行临床评分的日常评估和神经病理分子分析，我们观察到与对照组相比，AA 治疗组的严重程度较低，尤其是在疾病发作的早期阶段。我们还观察到 AA 治疗组的星形胶质细胞增生、脱髓鞘、免疫浸润、促炎细胞因子表达和酶促氧化反应性显著降低。总的来说，我们的结果强化了 S100B 在多发性硬化症动物模型发展中的作用，并提出针对 S100B 蛋白的 AA 靶向治疗作为一种有针对性的潜在药物来考虑多发性硬化症的治疗。
