Studying mechanisms of cell death: from apoptosis to necrosis

• Published in: The FASEB journal 2007-04, Vol.21 (5), p.A38-A38
• Main Authors: Yuan, Junying, Degterev, Alexei, Huang, Zhihong, Jagtap, Prakash, Cuny, Greg, Moskowitz, Michael
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.5.A38-d

The mechanism of apoptosis has been extensively characterized over the past decade. However, increasing evidence suggests that apoptosis is not the only cellular pathway of suicide. Although stimulation of Fas/TNFR receptor family by their corresponding ligands triggers a canonical “extrinsic” apoptosis pathway, we demonstrate that in the absence of intracellular apoptotic signaling it is capable of activating a common non‐apoptotic death pathway, which we term necroptosis. We show that necroptosis is characterized by necrotic cell death morphology and activation of autophagy. We identified a specific and potent small molecule inhibitor of necroptosis, Necrostatin‐1, which blocks a critical step in necroptosis. We demonstrate that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a novel therapeutic target for stroke with an extended window for neuroprotection. We propose that necroptosis is a novel basic cell death pathway with potentially broad relevance to human pathologies.