Matrix metalloproteinase-9 in glutamate-dependent adult brain function and dysfunction

Abstract

Matrix metalloproteinase-9 (MMP-9) is extracellularly operating protease that is expressed by the adult brain neurons and released in response to enhanced neuronal activity driven by glutamate. In addition, MMP-9 can also be produced by glial and endothelial cells as well as by infiltrating leukocytes. Extracellularly, the protein is activated in a cascade of steps that involves also other proteases and then is inhibited by tissue inhibitors of matrix metalloproteinases (TIMPs). Under physiological conditions, MMP-9 is involved in neuronal plasticity, including long-term potentiation as well as learning and memory. This function of MMP-9 may relate to its synaptic action that is a consequence of post-synaptic/dendritic locus of mRNA and protein storage and release. Under pathological conditions that involve excessive function of glutamate, such as excitotoxicity, stroke and traumatic brain injury, MMP-9 is detrimental to the brain tissue, probably because of its excessive activity. This complex functionality and dysfunctionality of MMP-9 is well documented by studies on its expression patterns as well as with an aid of chemical inhibitors and knockout mice.Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that together with the most closely related MMP-2, forms a subfamily of gelatinases.1,2 MMPs operate extracellularly (predominantly secreted pericellularly, and some membrane-bound) and are locally inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs) that bind MMPs non-covalently.

Yin Yang 1 Is a Critical Repressor of Matrix Metalloproteinase-9 Expression in Brain Neurons

“…Hence, MMP-9 is the first YY1-dependent gene identified in the adult neurons. It codes for an enzyme engaged in the regulation of neuronal plasticity (52)(53)(54) and can also contribute to neuronal cell death in pathological conditions (55). Thus, our data suggest that YY1 can also be implicated in neuronal plasticity as well as in neurodegeneration.…”

Increased Expression of Matrix Metalloproteinase-9 in Patients with Temporal Lobe Epilepsy

“…MMPs are a large family of zinc dependent proteinases that are considered major elements conducting the extracellular matrix (ECM) remodeling and have pivotal role in cancer invasion and metastasis (1,34). Many studies have identified that MMPs are associated with various central nervous system (CNS) pathologies including stroke, traumatic brain injury, cerebral arteriovenous malformation, influenza associated encephalopathy and in bacterial meningitis where it has been identified as a risk factor for developing neurological sequel (8,22,39). Moreover, many studies have reported that MMP-9 has implication in synaptic plasticity, learning and memory (21,25,28,36).…”

EffectsofLuteolinonLiver,KidneyandBraininPentylentetrazol-Induced Seizures: Involvement of Metalloproteinases and NOS Activities

“…The extensive data indicate that MMP9 is a molecule of great importance for neuronal physiology and pathology. Its activation appears to be intimately linked to glutamate acting as a potent neurotoxin (37). Recent studies indicate that MMP9 is an important participant in aberrant plasticity and neuroinflammation and neuronal death and it is upregulated in experimental epilepsy models (38).…”