Blockage of MLKL prevents myelin damage in experimental diabetic neuropathy

Abstract

Significance Diabetic neuropathy is a commonly occurring complication of diabetes that affects hundreds of millions of patients worldwide. Patients suffering from diabetic neuropathy experience abnormal sensations and have damage in their peripheral nerve axons as well as myelin, a tightly packed Schwann cell sheath that wraps around axons to provide insulation and increases electrical conductivity along the nerve fibers. The molecular events underlying myelin damage in diabetic neuropathy are largely unknown, and there is no efficacious treatment for the disease. The current study, using a diabetic mouse model and human patient nerve samples, uncovered a molecular mechanism underlying myelin sheath damage in diabetic neuropathy and provides a potential treatment strategy for the disease.

Schwann cell necroptosis in diabetic neuropathy

“…In conclusion, the data presented by Guo et al. ( 1 ) indicate a therapeutic target in a rodent model that may be of potential future interest and clearly warrants further preclinical and clinical investigations.…”

“…In PNAS, Guo et al. ( 1 ) explain how the necroptosis protein, mixed-lineage kinase domain–like protein (MLKL), causes Schwann cells to lose their function.…”

“…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 their current work, Guo et al. ( 1 ) first establish a transmission electron microscopy–based readout system of myelin decompaction following streptozotocin (STZ)–induced loss of pancreatic beta cells, thereby inducing diabetes. They demonstrate colocalization of MLKL with a known myelin sheath marker, indicating localization in the Schwann cells.…”