| | |  | | | | Record from Web of Science® | | | | | | |
| Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury |
|
|
| Author(s): Degterev A, Huang ZH, Boyce M, Li YQ, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan JY |
| Source: NATURE CHEMICAL BIOLOGY Volume: 1 Issue: 2 Pages: 112-119 Published: JUL 2005 |
| Times Cited: 149 References: 37 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
2. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA
3. Harvard Univ, Ctr Neurodegenerat & Repair, Lab Drug Discovery Neurodegenerat, Brigham & Womens Hosp, Cambridge, MA 02139 USA
4. Harvard Univ, Sch Med, Dept Syst Biol, Cambridge, MA 02139 USA
5. Tokyo Metropolitan Inst Med Sci, Dept Bioregulat & Metab, Tokyo 1138613, Japan |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 975GE |
| ISSN: 1552-4450 |
| DOI: 10.1038/nchembio711 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |