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Studying mechanisms of cell death: from apoptosis to necrosis
Author(s) -
Yuan Junying,
Degterev Alexei,
Huang Zhihong,
Jagtap Prakash,
Cuny Greg,
Moskowitz Michael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a38-d
Subject(s) - necroptosis , programmed cell death , apoptosis , microbiology and biotechnology , autophagy , neuroprotection , biology , signal transduction , necrosis , cancer research , neuroscience , genetics
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.