NDLI: Collagenase-2 deficiency or inhibition impairs experimental autoimmune encephalomyelitis in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fanjul-fernández, Miriam Gutiérrez-fernández, Ana Astudillo, Aurora Campestre, Cristina Overall, Christopher M. Edwards, Dylan R. García-suárez, Olivia Tortorella, Paolo Cox, Jennifer López-otín, Carlos Fueyo, Antonio Pennington, Caroline J. Folgueras, Alicia R.
Description	Author Affiliation: Folgueras AR ( Departamento de Bioquímica y Biología Molecular, and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, and Servicio de Anatomía Patológica, Hospital Central de Asturias, Oviedo 33006, Spain.)
Abstract	Matrix metalloproteinases (MMPs) have been implicated in a variety of human diseases, including neuroimmunological disorders such as multiple sclerosis. However, the recent finding that some MMPs play paradoxical protective roles in these diseases has made necessary the detailed study of the specific function of each family member in their pathogenesis. To determine the relevance of collagenase-2 (MMP-8) in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, we have performed two different analyses involving genetic and biochemical approaches. First, we have analyzed the development of EAE in mutant mouse deficient in MMP-8, with the finding that the absence of this proteolytic enzyme is associated with a marked reduction in the clinical symptoms of EAE. We have also found that MMP-8(-/-) mice exhibit a marked reduction in central nervous system-infiltrating cells and demyelinating lesions. As a second approach, we have carried out a pharmacological inhibition of MMP-8 with a selective inhibitor against this protease (IC(50) = 0.4 nM). These studies have revealed that the administration of the MMP-8 selective inhibitor to mice with EAE also reduces the severity of the disease. Based on these findings, we conclude that MMP-8 plays an important role in EAE development and propose that this enzyme may be a novel therapeutic target in human neuro-inflammatory diseases such as multiple sclerosis.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	14
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-04-04
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Central Nervous System Enzymology Encephalomyelitis, Autoimmune, Experimental Matrix Metalloproteinase 8 Metabolism Multiple Sclerosis Animals Pathology Chemically Induced Drug Therapy Genetics Matrix Metalloproteinase Inhibitors Mice Mice, Knockout Protease Inhibitors Pharmacology Therapeutic Use Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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