Recent findings implicate alterations in glutamate signaling, leading to aberrant synaptic plasticity, in schizophrenia. Matrix metalloproteinase-9 (MMP-9) has been shown to regulate glutamate receptors, be regulated by glutamate at excitatory synapses, and modulate physiological and morphological synaptic plasticity. By means of functional gene polymorphism, gene responsiveness to antipsychotics and blood plasma levels MMP-9 has recently been implicated in schizophrenia. This commentary critically reviews these findings based on the hypothesis that MMP-9 contributes to pathological synaptic plasticity in schizophrenia.Key words: synaptic plasticity/glutamate/extracellular matrix
Matrix Metalloproteinase-9 in Animal Studies
Matrix Metalloproteinase-9 Expression and Activity in the BrainMatrix metalloproteinase-9 (MMP-9) belongs to a family of zinc-dependent proteases, mostly secreted as inactive pro-enzymes, activated outside the cell upon proteolytic cleavage. MMPs degrade extracellular matrix constituents, other proteases, growth factors, and extracellular domains of transmembrane proteins, such as cell adhesion molecules and receptors. As a result, MMPs participate in remodeling the pericellular microenvironment and cell-signaling via either the release or processing (to reveal their binding domains) of cell-surface receptor ligands.