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

@article{Degterev2005ChemicalIO,
  title={Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury},
  author={Alexei Degterev and Zhihong Huang and Michael Boyce and Yaqiao Li and Prakash G. Jagtap and Noboru Mizushima and Gregory D. Cuny and Timothy J. Mitchison and Michael A. Moskowitz and Junying Yuan},
  journal={Nature Chemical Biology},
  year={2005},
  volume={1},
  pages={112-119}
}
The mechanism of apoptosis has been extensively characterized over the past decade, but little is known about alternative forms of regulated cell death. [...] Key Result 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.Expand
Double agents of cell death: novel emerging functions of apoptotic regulators
TLDR
This review outlines the convergence points between apoptosis and other death pathways with the purpose of identifying novel strategies for the treatment of apoptosis‐refractory cancers and raises the idea that a top‐to‐bottom approach to describing cell death mechanisms may be inadequate for fully understanding the means by which cells die.
Necroptosis is one of the modalities of cell death accompanying ischemic brain stroke: from pathogenesis to therapeutic possibilities
TLDR
By comparing various approaches in inhibition of necroptosis, the achieved effects from the perspective of controlling necroPTosis as a part of future therapeutic interventions in brain ischemia are analyzed.
Akt and mTOR mediate programmed necrosis in neurons
Necroptosis is a newly described form of regulated necrosis that contributes to neuronal death in experimental models of stroke and brain trauma. Although much work has been done elucidating
Necroptosis Signaling Pathways in Stroke: From Mechanisms to Therapies
TLDR
Re-cent advances in necroptosis are summarized, the mechanism and strategies targeting ne croptosis in stroke are introduced, and some issues in the treatment of stroke by targeting necroPTosis are proposed.
Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke
TLDR
Thorough interrogation of cellular pathways by saturation chemical genetics may provide a novel strategy to identify multiple key molecular entities that can be targeted chemically in order to select a target suitable for the treatment of intended human diseases such as stroke.
Perspectives on the therapeutic modulation of an alternative cell death, programmed necrosis (review).
  • Y. Cho
  • Biology, Medicine
    International journal of molecular medicine
  • 2014
TLDR
The significant advancement and state-of-art direction for the development of small molecules that can control programmed necrosis is discussed and the perspectives on novel strategies harnessing therapeutic targets identified thus far, are discussed.
Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury
TLDR
The state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury is reviewed recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models.
Necroptosis in cardiovascular disease - a new therapeutic target.
TLDR
This review delineates various genetic and biochemical evidence that demonstrates a compelling role of necroptosis in the pathogenesis and/or progression of cardiovascular disease including myocardial infarction, atherosclerosis, and aortic aneurysm.
Molecular Mechanisms of Apoptosis in Cerebral Ischemia: Multiple Neuroprotective Opportunities
TLDR
This review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators and their emerging roles in orchestrating cell death programme and the role of autophagy in modulating cell survival/death during cerebral ischemia.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 52 REFERENCES
Necrotic Death Pathway in FAS Receptor Signaling
TLDR
It is shown that the death effector domain of FADD is responsible for the FADD-mediated necrotic pathway, and the presence of z-VAD–fmk and pyrrolidine dithiocarbamate together blocked cell death, suggesting that both apoptotic and nec rotic pathways can be activated through the Fas death receptor.
Caspase-independent programmed cell death with necrotic morphology
TLDR
The existence of a necrotic-like cell death regulated by cellular intrinsic death programs distinct from that of apoptosis is suggested.
Tumor Necrosis Factor-induced Nonapoptotic Cell Death Requires Receptor-interacting Protein-mediated Cellular Reactive Oxygen Species Accumulation*
TLDR
This study utilized gene knockout mouse embryonic fibroblasts cells and found that tumor necrosis factor receptor (TNFR) I mediates TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical components of the signaling cascade of this TNF/NVC cell death.
Resistance to the Cytotoxic Effects of Tumor Necrosis Factor α Can Be Overcome by Inhibition of a FADD/Caspase-dependent Signaling Pathway*
TLDR
It is shown that caspase activation in response to TNFα has anti-necrotic as well as pro-apoptotic effects and this work extends the understanding of the biological role of these proteases.
More than one way to die: apoptosis, necrosis and reactive oxygen damage
TLDR
The distinguishing features of the various cell death pathways are reviewed: caspases (cysteine proteases cleaving after particular aspartate residues), mitochondria and/or reactive oxygen species are often, but not always, key components.
Intracellular ATP levels determine cell death fate by apoptosis or necrosis.
TLDR
This study addressed the question of whether apoptosis depends on intracellular ATP levels, since longer incubation under ATP-depleting conditions results in necrotic cell death, and indicated that ATP levels are a determinant of manifestation of cell death.
Fas triggers an alternative, caspase-8–independent cell death pathway using the kinase RIP as effector molecule
TLDR
F Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release.
A Role for Tumor Necrosis Factor Receptor-2 and Receptor-interacting Protein in Programmed Necrosis and Antiviral Responses*
TLDR
TNF-induced programmed necrosis is facilitated by TNFR-2 signaling and caspase inhibition and may play a role in controlling viral infection.
Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke
TLDR
Analysis of in vitro and in vivo models of ischemia reveals that inhibition of TNF and CD95L blocks stroke-related damage at two levels, the primary ischemic and the secondary inflammatory injury.
CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons
TLDR
An involvement of CD95 ligand and TRAIL in the pathophysiology of postischemic neurodegeneration is suggested and alternative strategies for the treatment of cardiovascular brain disease are offered.
...
1
2
3
4
5
...