A novel calpain inhibitor for the treatment of acute experimental autoimmune encephalomyelitis
A novel calpain inhibitor for the treatment of acute experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.jneuroim.2006.08.005
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发表时间：
2006-11-01
影响因子：
3.3
通讯作者：
Mokhtarian, Foroozan
中科院分区：
文献类型：
--
作者：
Hassen, Getaw Worku;Feliberti, Jason;Mokhtarian, Foroozan
钙蛋白酶的异常激活在多种神经退行性疾病的病理生理学中起着关键作用。在EAE的炎性细胞中，Calain的表达增加，在多发性硬化症患者的脑白质中表达显著升高，因此Calain的抑制可能成为治疗干预的靶点。本实验采用了一种髓鞘少突胶质细胞糖蛋白诱导的C57B1/6小鼠(EAE)疾病模型和一种针对神经组织的新型钙蛋白酶抑制剂。Cyla被发现可以减少EAE的临床症状，并以剂量和时间依赖的方式防止脱髓鞘和炎症浸润。口服双缩醛前药同样有效。(C)2006爱思唯尔B.V.保留所有权利。
Aberrant activation of calpain plays a key role in the pathophysiology of several neurodegenerative disorders. Calpain is increasingly expressed in inflammatory cells in EAE and is significantly elevated in the white matter of patients with multiple sclerosis, thus calpain inhibition could be a target for therapeutic intervention. The experiments reported here employed a myelin oligodendrocyte glycoprotein-induced disease model in C57B1/6 mice (EAE) and a novel calpain inhibitor, targeted to nervous tissue. CYLA was found to reduce clinical signs of EAE and prevent demyelination and inflammatory infiltration in a dose- and time-dependent manner. Oral administration of the diacetal prodrug was equally effective. (c) 2006 Elsevier B.V. All rights reserved.