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Cell death, particularly that of tubule epithelial cells, contributes critically to the pathophysiology of kidney disease. Over the past 15 years, a body of evidence has ascribed a central pathophysiological role to a particular form of regulated necrosis, termed necroptosis, to acute tubular necrosis, nephron loss and maladaptive renal failure fibrogenesis. Unlike apoptosis, a non-immunogenic process, necroptosis releases cellular contents and cytokines, which trigger an inflammatory response in neighbouring tissue. This necro-inflammatory environment can lead to severe organ dysfunction and cause lasting tissue injury in the kidney. Despite evidence of a link between necroptosis and various kidney diseases, there are no available therapeutic options to target this process. A greater understanding of the molecular mechanisms, triggers and regulators of necroptosis in acute and chronic kidney diseases may identify shortcomings in current approaches to therapeutically target necroptosis regulators and lead to the development of innovative therapeutic approaches.
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