title: Gelsolin decreases actin toxicity and inflammation in murine multiple sclerosis.
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.
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Li-ChunHsieh
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schob
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA.
authors.forename: Matthias W G
authors.initials: MW
authors.lastname: Zeller
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pulli
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Translational Medicine Division, Brigham & Women's Hospital, Harvard Medical School, MA, USA.
authors.forename: Terry Ting-Yu
authors.initials: TT
authors.lastname: Chiou
authors.affiliation: Division of Medical Imaging, Radiology Department, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Yuk-Ming
authors.initials: YM
authors.lastname: Tsang
authors.affiliation: Translational Medicine Division, Brigham & Women's Hospital, Harvard Medical School, MA, USA.
authors.forename: Po-Shun
authors.initials: PS
authors.lastname: Lee
authors.affiliation: Translational Medicine Division, Brigham & Women's Hospital, Harvard Medical School, MA, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Stossel
authors.affiliation: Center for Systems Biology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA, USA. Electronic address: jwchen@mgh.harvard.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D018260:Gelsolin / Q000378:metabolism* / Q000627:therapeutic use*; D005910:Glioma / Q000473:pathology; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000199:Actins; D039481:CD11b Antigen; D018260:Gelsolin; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D005620:Freund's Adjuvant; D009195:Peroxidase
keywords: Actin; Experimental autoimmune encephalomyelitis (EAE); Gelsolin; Inflammation; Magnetic resonance imaging; Myeloperoxidase