Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Degterev, A; Huang, Z; Boyce, M; Li, Y; Jagtap, P; Mizushima, N; Cuny, GD; Mitchison, TJ; Moskowitz, MA; Yuan, J

Published Date

  • July 2005

Published In

Volume / Issue

  • 1 / 2

Start / End Page

  • 112 - 119

PubMed ID

  • 16408008

Pubmed Central ID

  • 16408008

International Standard Serial Number (ISSN)

  • 1552-4450

Digital Object Identifier (DOI)

  • 10.1038/nchembio711

Language

  • eng

Conference Location

  • United States