- In vitro data available
- In vivo data available (animal)
Sirtuin 2 (SIRT2) inhibitors to reduce necrosis and, thereby, as novel therapeutics to treat ischemic stroke and myocardial infarction. Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. NIH investigators have shown that the NAD-dependent deacetylase SIRT2 binds constitutively to receptor-interacting protein 3 (RIP3) and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. These investigators also found that genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha and RIP1 is a critical target of SIRT2-dependent deacetylation. Further studies also showed that the hearts of Sirt2–/– mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischemic injury. These results implicate SIRT2 as an important regulator of programmed necrosis and indicate that SIRT2 inhibitors may constitute a novel approach to protect against necrotic injuries, including ischemic stroke and myocardial infarction.
- Novel therapeutics to protect against necrotic injuries.
- Novel therapeutics to treat ischemic stroke and myocardial infarction.
- Novel therapeutics to treat diseases in which necrosis is involved.
- None of the currently available drugs address the necrotic damage caused due to ischemia and reperfusion.
- Using a Sirt2 inhibitor could limit the damage caused by necrosis and contribute to accelerated recovery in patients suffering from these conditions.