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Studies from Dr. Xiaodong Wang’s laboratory reveal the mechanism of myelin breakdown in injured nerves.

Publication Date:2018/11/19

Myelin is a fatty material formed by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS) that protects and insulates axons to enhance their transmission of electrical impulses. When a PNS axon is severed from the cell body, the axon distal to the injury starts to degenerate by an active process called Wallerian degeneration, and the Schwan cell undergoes reprogramming to breakdown myelin and to promote axon regeneration. In a recent study (Ying et al., 2018, Molecular Cell), Dr. Wang’s group showed that MLKL, the prototype executioner of necroptotic cell death, is involved in the degradation of myelin sheaths following nerve injury.

MLKL, a pseudokinase discovered by Dr. Wang’s group (Sun et al., 2012, Cell), causes plasma membrane destabilization during necroptosis, a programmed form of inflammatory cell death. This process requires RIPK3-dependent phosphorylation of the C-terminal pseudokinase domain of MLKL. In the recent study, Ying and colleagues demonstrated that MLKL is expressed in Schwann cells of injured nerves. MLKL is then activated by a RIP3-independent phosphorylation event, and inserted into the myelin sheath where it breaks down myelin, thereby facilitating the removal of axon regeneration inhibitors in injured nerves. They also established that the forced expression of MLKL in injured nerves accelerates axon regeneration and promotes functional recovery of injured nerves, thus defining a therapeutic approach towards improved peripheral nerve regeneration.


Original research article: Zhengxin Ying, Chenjie Pan, Tianyu Shao, Liqing Liu, Lin Li, Dejia Guo, Sitao Zhang, Tianyi Yuan, Ran Cao, Zhaodi Jiang, She Chen, Fengchao Wang, and Xiaodong Wang. (2018). Mixed lineage kinase domain-like protein MLKL breaks down myelin following nerve injury. Molecular Cell 72, 457-468.

https://www.sciencedirect.com/science/article/pii/S1097276518307822