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Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview
S Chandler1, K M Miller, J M Clements
1British Biotech Pharmaceuticals Limited, Cowley, Oxford, UK.
Abstract:
The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process. MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.
Insights
Matrix metalloproteinases (MMPs) degrade extracellular matrix and process proteins, including tumor necrosis factor-alpha. MMPs contribute to inflammation and tissue damage in multiple sclerosis (MS), suggesting MMP inhibitors as potential therapies.
Area of Science:
- Biochemistry
- Immunology
- Neuroscience
Background:
- Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that degrade extracellular matrix proteins.
- MMPs also process cell surface proteins, including cytokines like tumor necrosis factor-alpha (TNF-α).
- TNF-α release from its membrane-bound precursor is an MMP-dependent process.
Purpose of the Study:
- To investigate the role of MMPs in the pathogenesis of multiple sclerosis (MS).
- To explore the potential of MMP inhibitors as therapeutic agents for MS.
Main Methods:
- Analysis of MMP expression in CNS lesions from animal models of MS and human MS patient tissue.
- Assessment of the efficacy of MMP inhibitors in animal models of MS.
Main Results:
- MMPs are expressed by inflammatory cells in CNS lesions associated with MS.
- MMP expression contributes to tissue destruction and inflammation in MS.
- MMP inhibitors demonstrate efficacy in animal models of MS.
Conclusions:
- MMPs play a significant role in the inflammatory processes and tissue damage observed in multiple sclerosis.
- Inhibition of MMP activity represents a promising therapeutic strategy for managing MS.