Matrix metalloproteinases in the adult brain physiology: a link between c-Fos, AP-1 and remodeling of neuronal connections?
Matrix metalloproteinases (MMPs), together with their endogenous inhibitors (TIMPs) form an enzymatic system that plays an important role in a variety of physiological and pathological conditions. These proteins are also expressed in the brain, especially under pathological conditions, in which glia as well as invading inflammatory cells provide the major source of the MMP activity. Surprisingly little is known about the MMP function(s) in adult neuronal physiology. This review describes available data on this topic, which is presented in a context of knowledge about the MMP/TIMP system in other organs as well as in brain disorders. An analysis of the MMP and TIMP expression patterns in the brain, along with a consideration of their regulatory mechanisms and substrates, leads to the proposal of possible roles of the MMP system in the brain. This analysis suggests that MMPs may play an important role in the neuronal physiology, especially in neuronal plasticity, including their direct participation in the remodeling of synaptic connections-a mechanism pivotal for learning and memory.
Kaczmarek
Leszek
L
Department of Molecular and Cellular Neurobiology, Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland. leszek@nencki.gov.pl
Lapinska-Dzwonek
Joanna
J
Szymczak
Sylwia
S
D000818:Animals; D001921:Brain / Q000201:enzymology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009422:Nervous System Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D016760:Proto-Oncogene Proteins c-fos; D019714:Tissue Inhibitor of Metalloproteinases; D018808:Transcription Factor AP-1; D049030:Dystroglycans; D020782:Matrix Metalloproteinases