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matrix metalloproteinases

By Ed Hill.

Matrix metalloproteinases (MMPs) are a group of proteins found all over the human body. They are responsible for breaking down and reforming bodily tissue and perform garbage disposal functions by breaking down and removing dead matter. MMPs are active in wound healing, bone and tooth growth, ovulation, menstruation, nerve, muscle and blood vessel growth and many other functions.

However, MMPs are double-edged swords. They are also key elements in the destruction caused by multiple sclerosis and many other diseases, including arthritis, cancer, stroke, arteriosclerosis and ulcerative colitis.

MMPs belong to a group of substances known as enzymes. Enzymes are molecules in living tissue which speed up biological processes without themselves being destroyed in the process. In multiple sclerosis, MMPs or more precisely a specific part of their molecular structure, promote the damaging chemical reactions which contribute to the nerve damage which is the hallmark of the disease.

The name "matrix metalloproteinase" is derived from:

There are currently about 22 known MMPs in the human body.

Normally, MMPs are held in check by complementary proteins called Tissue Inhibitors of Metalloproteinases (TIMPs).

Structurally, an MMP resembles an open hand containing a potentially destructive zinc ion in its palm. An MMP in combination with a TIMP is like two hands with the fingers interlaced and closed over the ion. Removal of the TIMP activates the MMP by exposing the zinc. People with MS are known to have an imbalance of MMPs and TIMPs in their central nervous system.

White blood cells (leukocytes), the cells of the immune system, are a major source of MMPs.

In MS, MMPs facilitate the passage of immune system cells into the central nervous system by cutting paths through lining of the blood vessels (the endothelium). They also play an important role in demyelination - the breaking down of the insulating myelin layer that sheathes the nerve cells (neurons). It is possible that they also contribute to the damage to the long extensions of the nerves cells (the axons).

MMPs interact with the chemical signals (cytokines) emitted by leukocytes. MMPs are not themselves cytokines - they actually do the damage - but they influence cytokines and are influenced by them. In fact, one of the most commonly used drugs in multiple sclerosis, beta interferon (Rebif, Avonex and Betaseron), is itself a cytokine which is known to inhibit MMP production.

It is relatively recently that the role of MMPs in multiple sclerosis has been recognised. They are currently a very hot topic of study with over 1,000 papers on MMPs published each year. They are also considered to be a key target for future MS therapies.

Matrix Metalloproteinases links:
Matrix Metalloproteinases (MMPs)
Matrix MetalloProteinases In Multiple Sclerosis
Seeking new Treatments for a Puzzling Disease Feature
Molecular Demolition

© Ed Hill, Febuary 2002


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