NAD+ availability and proteotoxicity.

It has been shown that NAD(+) availability is important for neuronal survival following ischemia (Liu et al., Neuromolecular Med 11:28-42, 2009). It is proposed here that NAD(+) may also control proteotoxicity by influencing both formation and catabolism of altered proteins. It is suggested that low NAD(+) availability promotes synthesis of methylglyoxal (MG) which can induce formation of glycated proteins, ROS, and dysfunctional mitochondria. That glyoxalase overexpression and carnosine are both protective against MG and ischemic injury support this proposal. Recognition and elimination of altered proteins is enhanced by NAD(+) through effects on stress protein expression and autophagy.