Extracellular Proteases: Biological and Behavioral Roles in the Mammalian Central Nervous System

Extracellular proteases and their inhibitors have been implicated in both physiological and pathological states in the central nervous system (CNS). Given the presence of several classes of proteases, it is believed that each enzyme may undertake distinct biological roles. Some are indispensable for neuronal migration, neurite outgrowth and pathfinding, and synaptic plasticity. Others are required for neuronal death and tumor growth and invasion. Furthermore, studies from transgenic animals lacking or overexpressing one or more of the proteases have suggested that functional compensation and redundance among different members do exist. Normally, protease activity is tightly regulated by specific inhibitors to prevent disastrous proteolysis. Various insults can disrupt the fine control of proteolysis and cause pathological changes. Novel strategies have been attempted to maintain or restore protease-inhibitor homeostasis, thus minimizing damages to the CNS. They may provide us with effective therapeutic tools for fighting certain neurological disorders.