Alternate cell-death program identified

© 2005 Nature Publishing Group

Harvard University's Junying Yuan and colleagues identified a chemical that blocks a programmed cell-death pathway that is non-apoptotic. Yuan's study¹ shows that the chemical, necrostatin-1 (Nec-1), has no effect on apoptosis, only on this programmed necrosis-like death, which her team calls "necroptosis."

Apoptosis is triggered when ligands bind to members of the Fas/TNFR (tumor necrosis factor receptor) family of death-domain receptors, which turns on multiple caspases. But, the Fas/TNFR family can induce cell death even when caspase signaling, and therefore apoptosis, is inhibited. This cell death usually resembles necrosis rather than apoptosis.

Yuan's team screened approximately 15,000 compounds, looking for inhibitors of an alternate death pathway. When human cells were treated with tumor necrosis factor-α (a ligand for the Fas/TNFR family) and a pan-caspase inhibitor, most cells died a necrosis-like death, but one small molecule, Nec-1, prevented cells from dying. Nec-1 inhibits TNF-α-induced...