Novel GLP-1R/GIPR co-agonist "twincretin" is neuroprotective in cell and rodent models of mild traumatic brain injury.

Novel GLP-1R/GIPR co-agonist "twincretin" is neuroprotective in cell and rodent models of mild traumatic brain injury. Exp Neurol. 2016 Nov 11;: Authors: Tamargo IA, Bader M, Li Y, Yu SJ, Wang Y, Talbot K, DiMarchi RD, Pick CG, Greig NH Abstract Several single incretin receptor agonists that are approved for the treatment of type 2 diabetes mellitus (T2DM) have been shown to be neuroprotective in cell and animal models of neurodegeneration. Recently, a synthetic dual incretin receptor agonist, nicknamed "twincretin," was shown to improve upon the metabolic benefits of single receptor agonists in mouse and monkey models of T2DM. In the current study, the neuroprotective effects of twincretin are probed in cell and mouse models of mild traumatic brain injury (mTBI), a prevalent cause of neurodegeneration in toddlers, teenagers and the elderly. Twincretin is herein shown to have activity at two different receptors, dose-dependently increase levels of intermediates in the neurotrophic CREB pathway and enhance viability of human neuroblastoma cells exposed to toxic concentrations of glutamate and hydrogen peroxide, insults mimicking the inflammatory conditions in the brain post-mTBI. Additionally, twincretin is shown to improve upon the neurotrophic effects of single incretin receptor agonists in these same cells. Finally, a clinically translatable dose of twincretin, when administered post-mTBI, is shown to fully restore the visual and s...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research