The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease.

The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Research Abstract Details 

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The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Abstract Text:

Ryan A Adams,Jan Bauer,Matthew J Flick,Shoana L Sikorski,Tal Nuriel,Hans Lassmann,Jay L Degen,Katerina Akassoglou,

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (alpha(M)beta(2), CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen-Mac-1 interaction in fibrinogen-gamma(390-396A) knock-in mice or pharmacologically impeding fibrinogen-Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (gamma(377-395)) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen-Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the gamma(377-395) fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation.

The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Publishing Authors By Initials

RA Adams,J Bauer,MJ Flick,SL Sikorski,T Nuriel,H Lassmann,JL Degen,K Akassoglou,

For similar peptides: peptide fragments research abstracts see: peptides: peptide fragments research

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The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of experimental medicine

VOLUME: 204

Page Numbers: 571-82

Journal Abbreviation: J. Exp. Med.

ISSN: 0022-1007

DAY: 5

MONTH: 03

YEAR: 2007

The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Information

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LANGUAGE: eng

NlmUniqueID: 2985109

The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Keywords Mesh Terms:

KEYWORDS: Peptide Fragments

MESH TERMS: physiology

Chemical & Substance for Abstract: The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. Information

Substance Name: Fibrinogen

Registry Number: 9001-32-5

Grant and Affiliation Information for The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease.

AFFILIATION: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R01 NS052189

ACRONYM: NS

MEDLINETA: J Exp Med

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