壞死性凋亡，又叫程序性壞死，是一種受調控的由RIP1和RIP3激酶介導的壞死性細胞死亡方式。壞死性凋亡的特徵包括：細胞質膜完整性會在早期丟失，細胞內容物洩漏，以及細胞器腫脹。通過壞死性凋亡方式死亡的細胞缺乏典型的凋亡特徵，例如，細胞膜出泡，染色質固縮和核小體內DNA裂解成180 bp的梯狀DNA，但也可能表現出TUNEL陽性。
Necroptosis is a form of regulated necrotic cell death mediated by RIP1 kinase and RIP3. Necroptosis is characterized by early loss of plasma membrane integrity, leakage of intracellular contents, and organelle swelling. The cells dying through necroptosis lack the typical apoptotic characteristics, such as membrane blebbing, chromatin condensation, and intranucleosomal DNA cleavage into 180 bp DNA laddering, but may show TUNEL positivity.
壞死性凋亡作為一種調節性壞死的細胞死亡形式的建立，顛覆了傳統的觀念，即壞死只能是壓倒性壓力造成的被動過程。如表所述，壞死性凋亡可由已知的激活炎症和細胞死亡的細胞外刺激觸發。RIP1激酶是該途徑關鍵的上遊調節因子，它通過多種磷酸化和泛素化事件來發揮複雜的調控作用，這些事件決定了細胞的生死命運。壞死性凋亡的細胞內信號傳導途徑涉及複合物IIb或壞死小體的形成，其中RIP1激酶結合併激活RIP3。壞死性凋亡的執行步驟涉及通過磷酸化激活假激酶MLKL，從而導致MLKL易位至質膜和細胞質膜（plasma and cytoplasmic membranes），從而調節離子通道活性導致壞死。
The establishment of necroptosis as a form of regulated necrotic cell death overturned the traditional belief that necrosis could only be a passive process caused by overwhelming stress. Necroptosis can be triggered by extracellular stimuli known to activate inflammation and cell death as summarized in the table. RIP1 kinase, a key upstream regulator of the pathway, is modulated intricately by multiple phosphorylation and ubiquitination events, which dictate the cellular fate to life or death. The intracellular signaling pathway of necroptosis involves the formation of complex IIb or necrosome, wherein RIP1 kinase binds and activates RIP3. The execution step of necroptosis involves the activation of pseudokinase MLKL by phosphorylation, resulting in MLKL translocation to the plasma and cytoplasmic membranes where it modulates ion channel activities to lead to necrosis.
在許多涉及細胞死亡和炎症的疾病的小鼠模型中，如在大腦，心臟，視網膜和腎臟的急性缺血再灌注損傷中，已經證明，抑制壞死性凋亡可以減輕小鼠的病理狀態。創傷性腦損傷；年齡相關性黃斑變性；動脈粥樣硬化炎症性腸病；高雪氏病；和同種異體排斥反應。抑制壞死性凋亡可能為治療多種涉及炎症和細胞死亡的人類疾病提供益處。
Inhibition of necroptosis has been shown to mitigate pathology in mouse models of numerous diseases involving cell death and inflammation, such as acute ischemiareperfusion injury in the brain, heart, retina, and kidney; traumatic brain injury; age-related macular degeneration; atherosclerosis; inflammatory bowel disease; Gaucher’s disease; and allograft rejection. Inhibition of necroptosis might provide benefits to the treatment of multiple human diseases involving inflammation and cell death.