Chemical regulation of signaling pathways to programmed necrosis.
Necroptosis is an active and well-orchestrated necrosis, distinctive from apoptosis in microscopic structure, and biochemical and molecular features. Unlike apoptosis-undergoing cells, which are removed by macrophage or neighboring cells, necrotic cell death releases danger signals and provokes inflammation, and further a severe damage to neighbor tissue. A regulated necrosis, termed as necroptosis or programmed necrosis, is emerging as a new paradigm of cell death that can be activated when apoptotic machinery is genetically or pathogenically defective. It plays biological significances in pathogenesis of a variety of inflammatory diseases as well as in a beneficial innate immune defense mechanism. This review highlights the identification of hits against necroptosis, and comprehensive approaches to discovery of small molecules that regulate necroptotic cell death. Also, the signaling molecular mechanism of necroptosis and future clinical uses of necroptosis inhibitor will be described in brief.
College of Pharmacy, Keimyung University, 1000 Sindang-dong, Dalseo-gu, Daegu, 704-701, South Korea.
Ji Hyun
JH
Bae
Jung-Hyun
JH
Shim
Young Sik
YS
Cho
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019216:Metals, Heavy / Q000633:toxicity; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019216:Metals, Heavy; D014409:Tumor Necrosis Factor-alpha