Fig. 1.

Demyelination during DN involves MLKL-mediated damage of Schwann cells. In healthy individuals, the speed at which an electrochemical impulse propagates down a neural pathway, referred to as nerve conduction velocity, requires Schwann cells for electric neuronal isolation. In DN, demyelination of Schwann cells was recognized decades ago and is well known to clinically associate with the stocking-and-glove pattern frequently observed in diabetic patients. Currently, no treatment for DN is clinically available. Guo et al. (1) set out to investigate how Schwann cells lose their function. They report a critical pathophysiological contribution of MLKL, a pseudokinase and key mediator of necroptosis. In the STZ-induced murine model of diabetes and in patients suffering from DN, Schwann cell degradation is a common feature. In that model, MLKL-deficient or MLKL-mutant mice, and wild-type mice treated with the MLKL inhibitor TC013249, exhibited less demyelination.