Multiple Sclerosis Resource Centre
  • Home
  • MSRC Grand Opening 30/05/12
  • About MS
  • MSRC Services
  • Get Involved
  • MS Research News
  • MSRC Groups
  • Useful Resources
  • Welcome To Josephs Court, MS Centre Of Excellence
  • Advertising
  • Best Bet Diet Group
  • E-Newsletter
  • Contact Us
  • Investor in People
    You are here : Home » MS Research News » New Discoveries » Fibrinogen, Mac-1 and Microglia

    Fibrinogen, Mac-1 and Microglia

    A A A
    [Print this page]

    Share |


    Inhibiting Blood to Save the Brain
    A fibrous protein called fibrinogen, found in circulating blood and important in blood clotting, can promote multiple sclerosis (MS) when it leaks from the blood into the brain, triggering inflammation that leads to MS-related nerve damage. Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a fibrin-derived peptide that inhibits this specific inflammation process in mouse models of MS, reducing MS symptoms.

    “Current strategies to develop therapies to fight MS primarily target T cells,” said Katerina Akassoglou, Ph.D., assistant professor in UCSD’s Department of Pharmacology, whose study was published in the March 19 issue of Journal of Experimental Medicine. “Blood proteins have been neglected as a therapeutic target, but this research shows that a blood clotting factor is an important player in MS.”

    MS is an inflammatory disease that affects the central nervous system, causing symptoms such as loss of balance and muscle coordination, and changes in cognitive function. The disease is marked by loss of myelin, a material that coats nerve fibres. Past studies showed that the destruction of the myelin sheath is associated with the accumulation of fibrinogen deposits in the brain of human MS patients. In this study, Akassoglou and colleagues showed that fibrinogen is not merely associated with the damage in MS, but an active participant. Fibrinogen activates macrophage cells in the brain called microglia, causing inflammation which damages myelin.

    The scientists sought to design a therapeutic strategy that would block the damaging effects of fibrinogen without affecting its beneficial blood coagulation. Studying a mouse model, the researchers identified a specific receptor called Mac-1 that is expressed by microglial cells and binds to fibrinogen. Mice expressing a mutant form of fibrinogen that failed to bind Mac-1 had fewer inflammatory lesions and less severe MS symptoms. Blocking the interaction between Mac-1 and fibrinogen after the first episode of paralysis using the fibrin peptide prevented subsequent relapses. It also prevented further microglia activation and damage to myelin in the diseased mice, allowing them to survive with improved motor function.

    “Importantly, this approach blocks fibrin’s interaction with microglia, but not with platelets, so clotting wouldn’t be impacted,” said Akassoglou, adding that this potential MS therapy might also have applications to other blood-brain barrier diseases where blood leakage and microglia activation is present such as spinal cord injury, Alzheimer’s disease or stroke.

    Additional contributors to the paper include Ryan A. Adams, Shoana L. Sikorski and Tal Nuriel of UCSD’s Department of Pharmacology; Jan Bauer and Hans Lassmann, Center for Brain Research, Medical University of Vienna; and Matthew J. Flick and Jay L. Degen, Children’s Hospital Research Foundation and University of Cincinnati College of Medicine.

    Funding for the study was provided in part by the National Institute for Neurological Disorders and Stroke, part of the National Institutes of Health, and by the National Multiple Sclerosis Society.

    Source: Newswise © 2007 Newswise. All Rights Reserved.(22/03/07)

    © Multiple Sclerosis Resource Centre

    Related Items
    Abnormal Liver Tests and MS
    AlphaB-crystallin
    Aluminium and Multiple Sclerosis
    Antagonist compounds
    Antibodies, B Cells,T-Cell Activation, Immune Response
    Apolipoprotein D
    Bacteria & MS
    Biomarkers and MicroRNA
    Blood tests
    Bone Marrow Cells and MS Treatment
    Bowmann-Birk Inhibitor Concentrate (BBIC)
    Brain Atrophy, Lesion Loads, White and Grey Matter
    Brain Inflammation
    Brain Iron Deposits
    Calcium Binding Proteins
    Cerebro-Spinal Fluid & Spinal Cord
    Chronic Cerebrospinal Venous Insufficiency (CCSVI)
    CRMP-2
    CXCL1, 7, 12
    Cytokines & Chemokines
    Dendritic Cells
    Estrogen Receptors
    HDL
    HERV-Fc1
    Histamine and MS
    Hormones And MS Research
    Immunoglobulins
    Infections and Multiple Sclerosis Relapses
    Interleukin-1beta
    JAK-STAT inhibitors
    Kallikrein 6
    Lipids & MS
    Medical Imaging
    Mycoplasmas And Bacteria
    N-acetylglucosamine (GlcNAc) & Glucosamine
    Natural Interferon Beta
    Natural Killer Cells
    Nerve and Brain Cell Research
    Neurosteroids
    Olig 1 Gene Discovery
    Oligodendrocytes and Astrocytes
    Pesticides and Multiple Sclerosis
    PKC-theta
    Plasma Exchange
    Potential Viral Causes of MS
    Proteomics
    Recombinant Human Erythropoietin
    Regeneration Research
    RNA and RNAi
    Synthetic Small Molecules
    Technology
    Tetanus Vaccine and Possible MS Protection
    Tetramers
    The Blood Brain Barrier
    Tremors And MS
    Uric Acid
    Urinary Problems
    Vascular Function And MS
    Vision and MS


    Did you find this information useful? Would you like to comment on this page? Let us know what you think! We welcome all comments and feedback on any aspect of our website - please click here to contact us.