Prevention of axonal injury using calpain inhibitor in chronic progressive experimental autoimmune encephalomyelitis
| Autor: | Getaw Worku Hassen, Leo Kesner, Alfred Stracher, Foroozan Mokhtarian, Jason Feliberti |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Silver Staining
Encephalomyelitis Autoimmune Experimental Leupeptins Encephalomyelitis Nerve Tissue Proteins Severity of Illness Index Article Sodium Channels Myelin oligodendrocyte glycoprotein Mice medicine Animals Molecular Biology Glycoproteins Autoimmune disease Analysis of Variance biology Myelin-associated glycoprotein Calpain business.industry General Neuroscience Multiple sclerosis Experimental autoimmune encephalomyelitis Proteolytic enzymes medicine.disease Axons Mice Inbred C57BL Disease Models Animal Myelin-Associated Glycoprotein nervous system NAV1.6 Voltage-Gated Sodium Channel Phosphopyruvate Hydratase Immunology biology.protein Myelin-Oligodendrocyte Glycoprotein Neurology (clinical) business Myelin Proteins Developmental Biology |
| Zdroj: | Brain Research. 1236:206-215 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2008.07.124 |
| Popis: | Axonal injury is the major correlate of permanent disability in neurodegenerative diseases such as multiple sclerosis (MS), especially in secondary-progressive MS which follows 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, Na(v)1.6 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 (2 mg/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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect