Abstract
Gelsolin is the fourth most abundant protein in the body and its depletion in the blood has been found in multiple sclerosis (MS) patients. How gelsolin affects the MS brain has not been studied. We found that while the secreted form of gelsolin (pGSN) decreased in the blood of experimental autoimmune encephalomyelitis (EAE) mice, pGSN concentration increased in the EAE brain. Recombinant human pGSN (rhp-GSN) decreased extracellular actin and myeloperoxidase activity in the brain, resulting in reduced disease activity and less severe clinical disease, suggesting that gelsolin could be a potential therapeutic target for MS.
Keywords:
Actin; Experimental autoimmune encephalomyelitis (EAE); Gelsolin; Inflammation; Magnetic resonance imaging; Myeloperoxidase.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Actins / metabolism
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Actins / toxicity*
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Animals
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Brain / drug effects
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Brain / metabolism
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CD11b Antigen / metabolism
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Cell Line, Tumor
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Disease Models, Animal
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / etiology
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Freund's Adjuvant / toxicity
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Gelsolin / metabolism*
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Gelsolin / therapeutic use*
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Glioma / pathology
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Humans
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Mice
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / etiology
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Multiple Sclerosis / metabolism
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Multiple Sclerosis / pathology
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Mycobacterium tuberculosis / immunology
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Myelin Proteolipid Protein / toxicity
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Neutrophils / drug effects
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Neutrophils / metabolism
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Peptide Fragments / toxicity
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Peroxidase / metabolism
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Time Factors
Substances
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Actins
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CD11b Antigen
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Gelsolin
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Myelin Proteolipid Protein
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Peptide Fragments
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myelin proteolipid protein (139-151)
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Freund's Adjuvant
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Peroxidase