New evidence for secondary axonal degeneration in demyelinating neuropathies

Neurosci Lett. 2021 Jan 23:744:135595. doi: 10.1016/j.neulet.2020.135595. Epub 2020 Dec 24.


Development of peripheral nervous system (PNS) myelin involves a coordinated series of events between growing axons and the Schwann cell (SC) progenitors that will eventually ensheath them. Myelin sheaths have evolved out of necessity to maintain rapid impulse propagation while accounting for body space constraints. However, myelinating SCs perform additional critical functions that are required to preserve axonal integrity including mitigating energy consumption by establishing the nodal architecture, regulating axon caliber by organizing axonal cytoskeleton networks, providing trophic and potentially metabolic support, possibly supplying genetic translation materials and protecting axons from toxic insults. The intermediate steps between the loss of these functions and the initiation of axon degeneration are unknown but the importance of these processes provides insightful clues. Prevalent demyelinating diseases of the PNS include the inherited neuropathies Charcot-Marie-Tooth Disease, Type 1 (CMT1) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and the inflammatory diseases Acute Inflammatory Demyelinating Polyneuropathy (AIDP) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Secondary axon degeneration is a common feature of demyelinating neuropathies and this process is often correlated with clinical deficits and long-lasting disability in patients. There is abundant electrophysiological and histological evidence for secondary axon degeneration in patients and rodent models of PNS demyelinating diseases. Fully understanding the involvement of secondary axon degeneration in these diseases is essential for expanding our knowledge of disease pathogenesis and prognosis, which will be essential for developing novel therapeutic strategies.

Keywords: AIDP; Acute inflammatory demyelinating polyneuropathy; CIDP; CMT; CMT1A; CMT1B; CMT1C; CMT1D; CMT1E; CMT1F; CMT1X; Charcot-Marie-Tooth disease; Chronic inflammatory demyelinating polyneuropathy; Cx32; Demyelination; EGR2; GBS; GJB1; Guillain-Barré syndrome; HNPP; Hereditary; LITAF/SIMPLE; MPZ; Myelin; NEFL; Neuropathy with liability to pressure palsies; PMP22; Peripheral neuropathy; Secondary axon degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Arthrogryposis / metabolism
  • Arthrogryposis / pathology
  • Axons / metabolism*
  • Axons / pathology
  • Charcot-Marie-Tooth Disease / metabolism
  • Charcot-Marie-Tooth Disease / pathology
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / pathology
  • Hereditary Sensory and Motor Neuropathy / metabolism
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Humans
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Polyneuropathies / metabolism*
  • Polyneuropathies / pathology
  • Schwann Cells / metabolism
  • Schwann Cells / pathology

Supplementary concepts

  • Tomaculous neuropathy