THE ROLE OF THROMBIN-LIKE (SERINE) PROTEASES IN THE DEVELOPMENT, PLASTICITY AND PATHOLOGY OF THE NERVOUS-SYSTEM

There is increasing evidence suggesting that members of the serine pro tease family, including thrombin, chymotrypsin, urokinase plasminogen activator, and kallikrein, may play a role in normal development and/o r pathology of the nervous system. Serine proteases and their cognate inhibitors have been shown to be increased in the neural parenchyma an d cerebrospinal fluid following injury to the blood brain barrier. Zym ogen precursors of thrombin and thrombin-like proteases as well as the ir receptors have also been localized in several distinct regions of t he developing or adult brain. Thrombin-like proteases have been shown to exert deleterious effects, including neurite retraction and death, on different neuronal and non-neuronal cell populations in vitro. Thes e effects appear to be mediated through cell surface receptors and can be prevented or reversed with specific serine protease inhibitors (se rpins). Furthermore, we have recently shown that treatment with protea se nexin-1 (a serpin that inhibits thrombin-like proteases) promotes t he survival and growth of spinal motoneurons during the period of prog rammed cell death and following injury. Taken together, these observat ions suggest that thrombin-like proteases play a deleterious role, whe reas serpins promote the development and maintenance of neuronal cells . Thus, changes in the balance between serine proteases and their cogn ate inhibitors may lead to pathological states similar to those associ ated with some neurodegenerative diseases such as Alzheimer's disease. The present review summarizes the current state of research involving such serine proteases and speculates on the possible role of these th rombin-like proteases in the development, plasticity and pathology of the nervous system. (C) 1997 Elsevier Science B.V.