Prevention of axonal injury using calpain inhibitor in chronic progressive experimental autoimmune encephalomyelitis.
Prevention of axonal injury using calpain inhibitor in chronic progressive experimental autoimmune encephalomyelitis.
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DOI：
10.1016/j.brainres.2008.07.124
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发表时间：
2008-10-21
期刊：
影响因子：
2.9
通讯作者：
Mokhtarian, Foroozan
中科院分区：
文献类型：
--
作者：
Hassen, Getaw Worku;Feliberti, Jason;Kesner, Leo;Stracher, Alfred;Mokhtarian, Foroozan
轴突损伤是神经退行性疾病如多发性硬化症(MS)，特别是复发-缓解病程后的继发性进展性MS的主要致残性因素。蛋白水解酶，钙蛋白酶，是引起轴突损伤的潜在候选者。目前的大多数治疗方案只针对MS的炎症成分。我们实验室以前使用Calain抑制剂Cyla的研究显示，急性实验性自身免疫性脑脊髓炎(EAE)的临床体征、脱髓鞘和组织Calain含量显著减少。在此，我们用组织学方法评估了慢性EAE[髓鞘少突胶质细胞糖蛋白(MOG)诱导的MS疾病模型]轴突损伤的标志物(淀粉样前体蛋白，Nav1.6通道)、神经元钙蛋白含量以及Cyla对轴突保护的影响。腹腔注射Cyla(2 mg/只/天)可明显减轻EAE的临床症状、组织钙蛋白含量、脱髓鞘和炎性细胞浸润。同样，在接受治疗的小鼠中，几乎检测不到轴突损伤的标志。因此，这种显著抑制病程、轴突损伤及其进展的新药是治疗多发性硬化症等神经退行性疾病的候选药物。
Axonal injury is the major correlate of permanent disability in neurodegenerative diseases such as multiple sclerosis (MS), especially in secondary-progressive MS following relapsing-remitting disease course. Proteolytic enzyme, calpain, is a potential candidate for causing axonal injury. Most current treatment options only target the inflammatory component of MS. Previous work using calpain inhibitor CYLA in our laboratory showed significant reduction in clinical sign, demyelination and tissue calpain content in acute experimental autoimmune encephalomyelitis (EAE). Here we evaluated markers of axonal injury (amyloid precursor protein, Nav1.6 channels), neuronal calpain content and the effect of CYLA on axonal protection using histological methods in chronic EAE [myelin oligodendrocyte glycoprotein (MOG) – induced disease model of MS]. Intraperitoneal application of CYLA (2mg/mouse/day) significantly reduced the clinical signs, tissue calpain content, demyelination and inflammatory infiltration of EAE. Similarly, markers for axonal injury were barely detectable in the treated mice. Thus, this novel drug, which markedly suppresses the disease course, axonal injury and its progression, is a candidate for the treatment of a neurodegenerative disease such as multiple sclerosis.
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影响因子：
3.3
作者：
Hassen, Getaw Worku;Feliberti, Jason;Mokhtarian, Foroozan
通讯作者：
Mokhtarian, Foroozan
影响因子：
14.5
作者：
BARNES, D;MUNRO, PMG;MCDONALD, WI
通讯作者：
MCDONALD, WI
影响因子：
4.8
作者：
Gafni, J;Hermel, E;Ellerby, LM
通讯作者：
Ellerby, LM
影响因子：
12.7
作者：
Diaz-Sanchez, M;Williams, K;Esiri, MM
通讯作者：
Esiri, MM
影响因子：
14.5
作者：
De Stefano, N;Matthews, PM;Arnold, DL
通讯作者：
Arnold, DL