Scientists from the Institute of Experimental Biology M. Nencki PAN were the first in the world to discover the role of the MMP-9 enzyme in the development of epilepsy in rodents. Their discovery gives hope for the development of new drugs for people suffering from epilepsy in the future.
Researchers have observed that in some synapses of the brain there is the MMP-9 enzyme, which digests other proteins outside of cells, and its excess increases the risk of developing epilepsy.
Our experiments have demonstrated the existence of a new mechanism of synaptic action and epilepsy development. This is the basis for starting research on the role of MMP-9 in epilepsy in humans, told PAP Dr. Grzegorz Wilczyński, head of the Laboratory of Neuromorphology at the Institute of Experimental Biology. M. Nencki PAN. The obtained results are the fruit of cooperation between the team of Dr. Wilczyński and the team of prof. Leszek Kaczmarek from the same Institute.
Nerve cells connect with each other through synapses, i.e. specialized membrane structures between which there is an intersynaptic space, into which various transmitters (neurotransmitters) are released, which play a fundamental role in transmitting nerve impulses. How active our brain is depends on how synapses work. For example, when learning something new, some of the synaptic connections become stronger, which is called a memory trace.
Synapses change in the course of thought processes – the strength of their transmission increases, they can stretch and contract, and this is what we call plasticity – explained Dr. Wilczyński.
There are several mechanisms responsible for synaptic plasticity and they are mainly related to changes in neurotransmitter receptors and changes in proteins, which are part of the cytoskeleton responsible for synapse movement. Scientists noticed that some of the synapses about to change grew rapidly, pushing themselves apart around them.
They put forward the thesis that synapses secrete a substance that digests and destroys structures that limit their movement. Suspicion fell on proteolytic enzymes that digest proteins. In this way, a mechanism was discovered that had so far not been taken into account when working on the brain and synapses.
MMP-9 is an extracellular matrix metalloproteinase 9, the scientist said. – Its protein digesting effect depends on zinc ions. Further studies showed that this enzyme is synthesized by nerve cells.
Moreover – continues Dr. Wilczyński – MMP-9 is present only in some synapses. For now, we don’t know why it is present in some and not in others. We only know that when the brain is stimulated, the percentage of synapses containing MMP-9 increases several times.
Synaptic plasticity, i.e. contraction and stretching, plays an important role not only in the learning process, but also in synaptic diseases. One of them is epilepsy. Here, the changes in synapses are more pronounced than in the learning processes. We believe that after brain damage, stroke or inflammation, there may be excessive production of the MMP-9 enzyme in synapses, the researcher adds.
Scientists from the Institute of Experimental Biology M. Nencki PAN conducted research on rodents. In transgenic mice lacking the gene encoding MMP-9, it turned out that the plastic changes were significantly weaker. In rats that produced more MMP-9 due to genetic modification, plastic changes increased, increasing the frequency of epileptic episodes.
However, many years of research are needed to find out whether inhibition of the MMP-9 enzyme in humans will reduce epilepsy. First, it is necessary to clarify whether the discoveries from the animal model translate into human life.
Detailed research must be carried out, starting with checking whether MMP-9 is in the synapses of the human brain and whether the amount of this enzyme increases in the brain of people suffering from epilepsy – emphasizes Dr. Grzegorz Wilczyński.
The work is in progress – adds the scientist. “But even assuming we get a positive answer, clinical trials will take many years. In addition to the fact that active therapies in animal models do not often work in humans, there are many types of epilepsy. We study temporal epilepsy, the most common epilepsy in adults. However, the role of MMP-9 cannot be expected to be important in all types of this disease. (PAP)