Proteases and degradation of extracellular matrix in neurodegeneration

Neurodegenerative diseases cause considerable morbidity and mortality throu ghout the world. Using an excitotoxin-induced model for neurodegeneration, the extracellular serine proteases tissue plasminogen activator (tPA) and p lasmin(ogen) have recently been implicated in neuronal death in the mouse h ippocampus. The search for plasmin substrates in the brain has revealed tha t the extracellular matrix (ECM) is an important factor influencing neurona l viability. The study of neuronal ECM proteins and the extracellular prote ases that act upon them could have important therapeutic implications for t he use of thrombolytics in stroke, and for the development of new treatment s for neurodegenerative disease. This review summarizes recent research eff orts that characterize the extracellular proteases and ECM proteins involve d in neuronal death, and relates the potential clinical significance.