Serine proteases and serpins: their possible roles in the motor system

A review of the importance of the extravascular fibrinolytic enzymes and their inhibitors in the neuromuscular system is discussed. We present data showing the role of specific serine proteases, the plasminogen activators, during neuromuscular development as well as after nerve injury and regeneration through their action on muscle basement membrane components. We show the presence in muscle of protease nexin I, a member of the serine protease inhibitors (serpins) family, where it is highly concentrated in the neuromuscular junction. These data have lead us to propose a model where the extravascular components of the fibrinolytic cascade and cellular derived serpins, such as protease nexin I, would act in the formation and maintenance of the neuromuscular synapse. Our conclusion is that future studies with these molecules, including their regulation at several levels, are warranted in a number of neuromuscular and neuro-degenerative diseases.