Extracellular proteases in epilepsy |
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Authors: | Lukasiuk Katarzyna Wilczynski Grzegorz M Kaczmarek Leszek |
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Affiliation: | Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St, 02-093 Warsaw, Poland |
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Abstract: | During the last decade, multiple data have been obtained, pointing to an involvement of extracellular, including extrasynaptic, proteolysis in epilepsy pathogenesis. The most productive avenues of investigations have been analyses of seizure-evoked gene and protein expression patterns, both hypothesis-driven and unbiased (e.g., DNA microarrays), complemented by functional analyses in animal models, as well as expression and gene polymorphism studies carried out on human tissue In result, serine proteases (e.g., tPA, thrombin, trypsin-like proteases, etc.), metalloproteinases, natural protease inhibitors, as well as complement components, and reelin have been identified as a novel molecular system, emerging as a key factor in the development of epilepsy, in addition to well known contribution of ion channels and signal transduction pathways. The extracellular location of the enzymes makes them particularly attractive potential targets for future pharmacological therapeutic interventions. |
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Keywords: | Abbreviations: ADAM, a disintegrin and metalloproteinase ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs CCI, controlled cortical impact ECM, extracellular matrix ECS, electroconvulsive shock FH, complement inhibitor GCD, granule cell dispersion KA, kainate or kainic acid LGI1, leucine-rich, glioma inactivated 1 LRP1, low density lipoprotein receptor-related protein 1 MAC, membrane-attack complexes MMP, matrix metalloproteinase PAI, plasminogen activator inhibitor PAR, protease activated receptor PTZ, pentylenetetrazol SE, status epilepticus TBI, traumatic brain injury TIMP, tissue inhibitor of matrix metalloproteinases TLE, temporal lobe epilepsy tPA, tissue type plasminogen activator uPA, urokinase type plasminogen activator uPAR, urokinase type plasminogen activator receptor VLDLR, very low density lipoprotein receptor |
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