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Faculty of Medicine
Document Details
Document Type
:
Article In Journal
Document Title
:
Neurofascin as a novel target for autoantibody-mediated axonal injury
Neurofascin as a novel target for autoantibody-mediated axonal injury
Document Language
:
English
Abstract
:
Axonal injury is considered the major cause of disability in patients with multiple sclerosis (MS), but the underlying effector mechanisms are poorly understood. Starting with a proteomics based approach we identified neurofascin (NF)-specific autoantibodies in patients with MS. These autoantibodies recognize the native form of the extracellular domains of both NF186, a neuronal protein concentrated in myelinated fibers at nodes of Ranvier, and NF155, the oligodendrocyte-specific isoform of neurofascin. Our in vitro studies with hippocampal slice cultures indicate that neurofascin antibodies inhibit axonal conduction in a complement dependent way. To evaluate whether circulating anti-neurofascin antibodies mediate a pathogenic effect in vivo we co-transferred these antibodies with myelin oligodendrocyte glycoprotein-specific encephalitogenic T cells to mimic the inflammatory pathology of MS and breach the blood-brain barrier. In this animal model antibodies to neurofascin selectively targeted nodes of Ranvier, resulting in deposition of complement, axonal injury and disease exacerbation. Together, these results identify a novel mechanism of immune mediated axonal injury that can contribute to axonal pathology in MS
ISSN
:
0022-1007
Journal Name
:
Journal of Experimental Medicine
Volume
:
204
Issue Number
:
10
Publishing Year
:
1428 AH
2007 AD
Article Type
:
Article
Added Date
:
Sunday, March 30, 2008
Researchers
Researcher Name (Arabic)
Researcher Name (English)
Researcher Type
Dr Grade
Email
عبدالمنعم الحياني
Al-Hayani, AbdulMonem
Researcher
Doctorate
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Type
Description
Neurofascin.pdf
pdf
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