Matrix metalloproteinases in neuroinflammation
Version of Record online: 18 JUL 2002
Copyright © 2002 Wiley-Liss, Inc.
Volume 39, Issue 3, pages 279–291, September 2002
How to Cite
Rosenberg, G. A. (2002), Matrix metalloproteinases in neuroinflammation. Glia, 39: 279–291. doi: 10.1002/glia.10108
- Issue online: 18 JUL 2002
- Version of Record online: 18 JUL 2002
- Manuscript Accepted: 8 MAY 2002
- Manuscript Received: 18 MAR 2002
- National Institutes of Health. Grant Number: RO1 21169
- matrix metalloproteinases;
Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders. GLIA 39:279–291, 2002. © 2002 Wiley-Liss, Inc.