Nascimento Pires Greice, Pereira Laurindo Renata, Dos Santos Heringer Luiza, Calixto da Silva Stefanny, Magalhães Portela Débora, Cardoso Ricardo, de Pádua Ana Carolina, Miranda De Sá Ana Beatriz, Alves Da Cruz Saulo Augusto, Espírito Santo Araújo Sheila, Blanco Martinez Ana Maria, Batista Carneiro Milena, Rocha Mendonça Henrique
Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Street Prof. Rodolpho Paulo Rocco 255 - Universitary City of the Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-617, Brazil; Integrated Lab of Morphology, Institute of Biodiversity and Sustainability NUPEM, Multicentric Postgraduate Program in Physiological Sciences - SBFis, Federal University of Rio de Janeiro, Avenue Amaro Reinaldo dos Santos Silva, 764 - São José do Barreto, Macaé, RJ 27965-045, Brazil.
Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Street Prof. Rodolpho Paulo Rocco 255 - Universitary City of the Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-617, Brazil.
Neurotoxicology. 2025 Mar;107:37-52. doi: 10.1016/j.neuro.2025.01.004. Epub 2025 Jan 31.
Inflammatory demyelination is present in debilitating diseases such as Multiple Sclerosis (MS). Several drugs are available for MS treatment, with fingolimod as a first-line oral option in the United States. However, a cure has yet to be established, and therapeutic failures are common, highlighting the need for continued research into new pharmacological targets. Pranlukast has shown positive effects on myelination in cell cultures and after LPC-induced demyelination in mice, but it is not yet part of the therapeutic arsenal for this disease. This study investigates pranlukast's effect on demyelination protection in an MS animal model, compared to fingolimod. For this purpose, young adult Swiss mice were treated for five weeks with a 0.2 % cuprizone diet and received daily intraperitoneal injections of pranlukast (0.1 mg/kg), fingolimod (1 mg/kg), or vehicle. Pranlukast treatment, like fingolimod, partially preserved sensory function in the tactile sensitivity test. Both treatments partially preserved myelin basic protein (MBP) levels, but only fingolimod preserved lipids and myelinated fibers in the corpus callosum (CC) at all g-ratio ranges. Cuprizone and Pranlukast groups presented more microglia/macrophages in the CC, but fewer presenting reactive microglia/macrophages and less NOS2 staining in pranlukast-treated when compared to the cuprizone group, while fingolimod treatment prevented the increase in Iba1 in the CC. In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment.
炎症性脱髓鞘存在于诸如多发性硬化症（MS）等使人衰弱的疾病中。有几种药物可用于MS治疗，在美国，芬戈莫德是一线口服药物选择。然而，尚未找到治愈方法，治疗失败很常见，这凸显了继续研究新的药理学靶点的必要性。普仑司特在细胞培养以及小鼠LPC诱导的脱髓鞘后对髓鞘形成显示出积极作用，但它尚未成为该疾病治疗手段的一部分。本研究将普仑司特与芬戈莫德相比，调查其在MS动物模型中对脱髓鞘保护的作用。为此，将年轻成年瑞士小鼠用0.2%的曲吡酮饮食治疗五周，并每天腹腔注射普仑司特（0.1mg/kg）、芬戈莫德（1mg/kg）或赋形剂。与芬戈莫德一样，普仑司特治疗在触觉敏感性测试中部分保留了感觉功能。两种治疗都部分保留了髓鞘碱性蛋白（MBP）水平，但只有芬戈莫德在所有g比值范围内都保留了胼胝体（CC）中的脂质和有髓纤维。曲吡酮组和普仑司特组在CC中出现了更多的小胶质细胞/巨噬细胞，但与曲吡酮组相比，普仑司特治疗组中呈现反应性小胶质细胞/巨噬细胞的较少，NOS2染色也较少，而芬戈莫德治疗可防止CC中Iba1增加。总之，本研究表明，普仑司特通过调节炎症环境恢复功能，是用于炎症性脱髓鞘疾病（如MS）的新型药物的良好候选者。
