Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response.

By N. Festjens, T. Vanden Berghe, Peter Vandenabeele. Biochimica et Biophysica Acta, 2006

737 citations recorded by the source corpus.

Necrosis has long been described as a consequence of physico-chemical stress and thus accidental and uncontrolled. Recently, it is becoming clear that necrotic cell death is as well controlled and programmed as caspase-dependent apoptosis, and that it may be an important cell death mode that is both pathologically and physiologically relevant. Necrotic cell death is not the result of one well-described signalling cascade but is the consequence of extensive crosstalk between several biochemical and molecular events at different cellular levels. Recent data indicate that serine/threonine kinase RIP1, which contains a death domain, may act as a central initiator. Calcium and reactive oxygen species (ROS) are main players during the propagation and execution phases of necrotic cell death, directly or indirectly provoking damage to proteins, lipids and DNA, which culminates in disruption of organelle and cell integrity. Necrotically dying cells initiate pro-inflammatory signalling cascades by actively releasing inflammatory cytokines and by spilling their contents when they lyse. Unravelling the signalling cascades contributing to necrotic cell death will permit us to develop tools to specifically interfere with necrosis at certain levels of signalling. Necrosis occurs in both physiological and pathophysiological processes, and is capable of killing tumour cells that have developed strategies to evade apoptosis. Thus detailed knowledge of necrosis may be exploited in therapeutic strategies.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/52d71e22cf29b68ea7732751db8df1aa238fd4d4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Molecular Biology

Citations in the corpus

Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. (2009, background): “Other systems in which morphologically defined necrosis occur include T lymphocytes after HIV-1 infection and neutrophils/macrophages after bacterial infection (Festjens et al., 2006).”
Lysosomal membrane permeabilization in cell death (2008, background): “In addition, the inhibition of specific proteins involved in regulating apoptosis or autophagy can change the morphological appearance of cell death to necrosis (Festjens et al., 2006; Golstein and Kroemer, 2007).”
Classification of cell death (2005, positive): “For a long time, necrosis has been considered merely as an accidental uncontrolled form of cell death, but evidence is accumulating that the execution of necrotic cell death may be finely regulated by a set of signal transduction pathways and catabolic mechanisms.(4,47) For instance, death domain re”
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions (2022, background): “Recent studies have reported necrosis to be a highly regulated process involving various signaling pathways.(200) The major downstream signaling pathways controlled by TNF-α include receptor-interacting protein kinase (RIPK1 and RIPK3) and mixed lineage kinase domain-like pathways.”
Cell death by necrosis: towards a molecular definition. (2007, background): “In this model, cells initiate a complex multistep signal transduction pathway in which Fas-associated death domain (FADD) is recruited to the (possibly endocytosed) TNF receptor 1 (TNF-R1) and induces necrosis, presumable through its death domain [ 3 ].”
Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis (2012, background): “Under certain conditions, the complex of TRADD, RIP1, and TRAF2 proteins dissociates from the receptor and recruits other proteins to form different secondary complexes to mediate apoptosis and necrosis (8, 9).”