Necrosis refers to a kind of cell injury that results in premature cell death by autolysis in living tissues. It is mainly caused by external or internal factors of cells and tissues, like infection and trauma leading to dysregulation of cell components digestion. Mostly, necrosis is a detrimental and even fatal process, while the naturally programmed process, apoptosis, is usually beneficial for the organism.
Unlike the apoptotic signal transduction pathway, necrosis leads to the activation of a wide range of receptors causing the loss of integrity of cell membranes and abnormal release of products into the extracellular space related to cell death. These processes cause inflammation responses in the neighboring tissue, attracting leukocytes and phagocytes to remove the dead cells, releasing microbial damaging components, thus bringing tissue damage nearby. Cell death caused by necrosis can be recognized by cell and organelle swelling, loss in integrity of plasma membrane, and nuclear condensation (pyknosis).
Morphologically, there are 6 patterns of necrosis:
Fig.1 Structural changes of cells undergoing necrosis and apoptosis.
Necrosis can be triggered by the activation of numerous modulators, including the molecules from the TNF receptor superfamily, Toll-like receptors (TLRs), interferon receptors, T cell receptors, cellular metabolic stresses, genotoxic stresses, as well as a variety of anti-cancer agents. On the other hand, necrosis can be suppressed by chemical compounds pharmacologically, like necrostatin-1 (Nec-1). Receptor-interacting protein kinase 1 (RIP1) and RIP3 mediate the formation of the “necrosome”, a process of multiple steps that involves 3 key checkpoints, which is demonstrated as one of the most essential characteristics of necroptosis. Necroptosis regulated by TNF is the most well-investigated form of necrosis. There are many molecules and pathways that participate in TNF receptor-mediated necroptosis, including but not limited to ROS, PARP1, cIAP1/2, AIF, Drp1, PGAM5, LMP process, FADD, NF-κB pathway, etc.
Necrosis plays a crucial role in normal development, and has been intensively associated with the pathogenesis of a broad spectrum of human diseases, including inflammatory diseases, osteonecrosis, autoimmune diseases like SLE, diabetes, cancers, etc. It has been recognized as an important prognostic factor and a therapeutic target. Necrosis assessment based on imaging techniques, histopathological examination, and biological assays are widely utilized in treatment, while therapeutic agents directed to targets and pathways in necrosis are also extensively being studied and applied.
As a pioneer in antibody research and development, Amerigo Scientific has gained rich knowledge and resources in
targeting various biological processes including necrosis, as well as the genes and pathways within. We are proud to introduce our antibody products for various applications to our esteemed clients around the world, please feel free to for more information.
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