853 Ueda et al. describe a protein that switches cells between two death mechanisms, preventing necrosis while promoting apoptosis. The molecule might provide a new way to save brain cells after a stroke.
A stroke delivers a double whammy. First, cells near the clot begin to perish from necrosis, which is triggered by ATP scarcity. Later, more distant cells start dying through apoptosis. Although anti-apoptosis compounds can stem some damage, their benefits are modest, possibly because the necrosis is more devastating. Molecules to halt necrosis have proven elusive.
Ueda et al. found one such molecule in cultures of rat cortical neurons. The protein ProTα curbs necrosis in cultures that lack serum or have been oxygen deprived. But it also boosts their apoptotic death rates. Adding growth factors that derail apoptosis protects most of the cells.
The group showed that ProTα works by keeping cells well-nourished. During necrosis, some of the GLUT transporters that usher glucose into the cell exit the plasma membrane. But ProTα prevents this relocation.
Ueda et al. conclude that ProTα flips cells from an uncontrollable form of cell death, necrosis, to a more controllable one. Other factors can derail cells from apoptosis. A treatment that mixes ProTα with some of these compounds might spare neurons after a stroke.