NEURONAL DEATH IN THE CENTRAL-NERVOUS-SYSTEM DEMONSTRATES A NON-FIBRIN SUBSTRATE FOR PLASMIN

Mice deficient for plasminogen exhibit a variety of pathologies, all o f which examined to date are reversed when the animals are also made f ibrin(ogen) deficient. These results suggested that the predominant, a nd perhaps exclusive, physiological role of plasminogen is clearance o f fibrin. Plasminogen-deficient mice also display resistance to excito toxin-induced neurodegeneration, in contrast with wild-type mice, whic h are sensitive. Eased on the genetic interaction between plasminogen and fibrinogen,,ve investigated whether resistance to neuronal cell de ath in the plasminogen-deficient mice is dependent on fibrin(ogen). Un expectedly, mice lacking both plasminogen and fibrinogen are resistant to neurodegeneration to levels comparable to plasminogen-deficient mi ce. Therefore, plasmin acts on substrates other than fibrin during exp erimental neuronal degeneration, and may function similarly in other p athological settings in the central nervous system.