MECHANISMS OF PRION(SC)- AND HIV-1 GP120 INDUCED NEURONAL CELL-DEATH

In vitro experiments revealed that the scrapie prion protein, PrPSc, a s well as the PrP fragment PrP106-126, and the HIV-1 coat protein gp 1 20 induce apoptosis of rat cortical neurons. The toxic effect displaye d by PrP and gp120 could be blocked by NMDA receptor antagonists. Trea tment of neuronal cells with PrP106-126 resulted in a drop of intracel lular glutathione level and changes in the level of Bcl-2. Evidence is presented that gp120 causes an activation of phospholipase A,, result ing in the increased release of arachidonic acid, which may in turn se nsitize the NMDA receptor. (C) 1998 Inter Press, Inc.