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