Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.
| dc.contributor.author | Degterev, Alexei | |
| dc.contributor.author | Huang, Zhihong | |
| dc.contributor.author | Boyce, Michael | |
| dc.contributor.author | Li, Yaqiao | |
| dc.contributor.author | Jagtap, Prakash | |
| dc.contributor.author | Mizushima, Noboru | |
| dc.contributor.author | Cuny, Gregory D | |
| dc.contributor.author | Mitchison, Timothy J | |
| dc.contributor.author | Moskowitz, Michael A | |
| dc.contributor.author | Yuan, Junying | |
| dc.date.accessioned | 2020-01-01T17:14:52Z | |
| dc.date.available | 2020-01-01T17:14:52Z | |
| dc.date.issued | 2005-07 | |
| dc.date.updated | 2020-01-01T17:14:52Z | |
| dc.description.abstract | The mechanism of apoptosis has been extensively characterized over the past decade, but little is known about alternative forms of regulated cell death. Although stimulation of the Fas/TNFR receptor family triggers a canonical 'extrinsic' apoptosis pathway, we demonstrated that in the absence of intracellular apoptotic signaling it is capable of activating a common nonapoptotic death pathway, which we term necroptosis. We showed 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 demonstrated that necroptosis contributes to delayed mouse ischemic brain injury in vivo through a mechanism distinct from that of apoptosis and offers a new therapeutic target for stroke with an extended window for neuroprotection. Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies. | |
| dc.identifier | nchembio711 | |
| dc.identifier.issn | 1552-4450 | |
| dc.identifier.issn | 1552-4469 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Nature chemical biology | |
| dc.relation.isversionof | 10.1038/nchembio711 | |
| dc.subject | Cell Line, Tumor | |
| dc.subject | Animals | |
| dc.subject | Humans | |
| dc.subject | Mice | |
| dc.subject | Brain Ischemia | |
| dc.subject | Imidazoles | |
| dc.subject | Indoles | |
| dc.subject | Protein-Serine-Threonine Kinases | |
| dc.subject | Tumor Necrosis Factor Receptor-Associated Peptides and Proteins | |
| dc.subject | Protein Kinase Inhibitors | |
| dc.subject | Signal Transduction | |
| dc.subject | Cell Death | |
| dc.subject | Molecular Structure | |
| dc.subject | Receptor-Interacting Protein Serine-Threonine Kinases | |
| dc.title | Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Boyce, Michael|0000-0002-2729-4876 | |
| pubs.begin-page | 112 | |
| pubs.end-page | 119 | |
| pubs.issue | 2 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Biochemistry | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.publication-status | Published | |
| pubs.volume | 1 |
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