A novel small molecule activator of sirtuins
Sirtuins are a family of protein deacetylases with demonstrated ability to suppress mechanisms of disease in several important contexts. A protective role for sirtuins has been demonstrated in diseases including myocardial ischemia, Alzheimer’s disease, aging, cancer and diabetes, amongst others. Given that sirtuin activity dampens inflammatory processes and promotes cellular metabolic homeostasis and survival, manipulation of this pathway could represent a novel mechanism to inhibit progression of diseases with an underlying inflammatory cell death component. The present technology relates to a method for increasing sirtuin activity within cells using a novel small molecule with proven anti-inflammatory and cardioprotective qualities.
This invention uses a novel small molecule to promote the expression and activity of sirtuins within cells. In both in vitro and in vivo models of cardimyocyte damage, treatment with this molecule increased sirtuin activity which was associated with enhanced cellular survival, and reduced activation of cell-intrinsic inflammatory pathways. This technology may therefore be useful as a novel cardioprotectant agent to be administered to patients during cardiac surgery, or immediately following myocardial damage due to myocardial infarction, etc.
Although tested primarily in cardiac protection, this invention may be useful for promoting cell survival and limiting inflammation in other disease contexts (i.e. Alzheimer’s, diabetes) in which sirtuins have been demonstrated to play a role.
Current methods for suppressing cardiac inflammation involves the use of systemic immunosuppressants, which have several severe side effects. This invention represents a novel method for inhibition of inflammation and promotion of cell survival which does not require concomitant systemic immunosuppression.