Researchers demonstrate both genetic and pharmaceutical evidence for the role of a protein called collagenase-2 in the development of multiple sclerosis (MS), providing a potential new way to combat this debilitating disease.
Collagenase-2 is a member of a protein family called matrix metalloproteinases (MMPs, collagenase-2 is MMP8), a large group of enzymes that break down collagen and other components of the body's connective tissue. MMPs have been implicated in contributing to MS by degrading the tissue that maintains the blood-brain barrier, thus allowing unwanted cells to invade and break down nerves. In fact, MMPs are found in elevated amounts in the blood and spinal fluid of diseased individuals.
Using a mouse model of MS, Carlos Lopez-Otin and colleagues performed two analyses on MMP8 to determine how relevant this protein is to the disease. First, they developed mutant mice deficient in the gene for MMP8 and found that these mice had a fewer invading cells in the brain, fewer damaged nerves, and a general improvement in their clinical profile.
They also gave diseased mice a drug that blocked MMP8 activity and found that this, too, could reduce the severity of disease symptoms. Taken together, these promising findings provide the first causal evidence for MMP8 in the development of MS, and offer a new therapeutic target.
This story appears in JBC online on March 28.
Corresponding Author: Carlos Lopez-Otin, Department of Biochemistry and Molecular Biology, Universidad de Oviedo, Spain; Phone: 34-985-104201, E-mail: clo@uniovi.es
Journal
Journal of Biological Chemistry