Abstract
Matrix metalloproteinase 9 is a proteolytic enzyme which is recently one of the more often studied biomarkers. Its possible use as a biomarker of neuronal damage in stroke, heart diseases, tumors, multiple sclerosis, and epilepsy is being widely indicated. In epilepsy, MMP-9 is suggested to play a role in epileptic focus formation and in the stimulation of seizures. The increase of MMP-9 activity in the epileptic focus was observed both in animal models and in clinical studies. MMP-9 contributes to formation of epileptic focus, for example, by remodeling of synapses. Its proteolytic action on the elements of blood-brain barrier and activation of chemotactic processes facilitates accumulation of inflammatory cells and induces seizures. Also modification of glutamatergic transmission by MMP-9 is associated with seizures. In this review we will try to recapitulate the results of previous studies about MMP-9 in terms of its association with epilepsy. We will discuss the mechanisms of its actions and present the results revealed in animal models and clinical studies. We will also provide a comparison of the results of various studies on MMP-9 levels in the context of its possible use as a biomarker of the activity of epilepsy.
Highlights
Discovered in 1974 matrix metalloproteinase 9 (MMP-9), known as gelatinase B, belongs to the superfamily of proteolytic enzymes, degrading extracellular matrix and influencing almost all aspects of mammalian cell biology
Apart from epilepsy models MMP-9 was observed to cause cell death contributing, for example, to impairment of transmission between extracellular matrix (ECM) and the cell through the lipoprotein receptor-related protein [107], separation of the cells from ECM leading to anoikis, the kind of apoptosis caused by the activation of proteolytic cascades [108], an increase of calpain activation [109], and initiation of caspase cascade and induction of cytotoxicity [77]
The researchers stated that these results suggest regulation of the levels of MMP-9 expression and activity by multiple activation of NMDA receptors [4]
Summary
Discovered in 1974 matrix metalloproteinase 9 (MMP-9), known as gelatinase B, belongs to the superfamily of proteolytic enzymes, degrading extracellular matrix and influencing almost all aspects of mammalian cell biology. According to proteomic research the number of possible substrates of MMP-9 may reach even a few hundred. Within the cell the presence of the active form of MMP-9 was confirmed in nucleus of neurons and glia [6, 7]. An increase of MMP-9 expression in neurons is induced by their depolarization and Mediators of Inflammation activation of receptors [14, 15]. Inflammatory factors cause the increase of MMP-9 expression [16, 17]. In human neural cells interleukin- (IL) 1β increases transcription of MMP-9 and transforming growth factor β (TGF-β) inhibits it [18]. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) increase expression and activity of MMP-9 [19, 20]. In paragraphs the effects of MMP-9 activity and its associations with epilepsy will be presented
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