[Calpain as a new therapeutic target for treating spasticity after a spinal cord injury]

Med Sci (Paris). Jun-Jul 2017;33(6-7):629-636. doi: 10.1051/medsci/20173306020. Epub 2017 Jul 19.
[Article in French]

Abstract

After a spinal cord injury (SCI), patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (I NaP), simultaneously with a disinhibition caused by a reduction of expression of chloride (Cl-) co-transporters KCC2. Until recently the origin of alterations was unknown. After reviewing pathophysiology of spasticity, the manuscript relates our recent work showing a tight relationship between the calpain-dependent proteolysis of voltage-gated sodium channels, the upregulation of I NaP and spasticity following SCI. We also discuss KCC2 as a substrate of calpains which may contribute to the disinhibition of motoneurons below the lesion. This led us to consider the proteolytic cleavage of both sodium channels and KCC2 as the upstream mechanism contributing to the development of spasticity after SCI.

Publication types

  • Review

MeSH terms

  • Animals
  • Calpain / antagonists & inhibitors
  • Calpain / physiology*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Muscle Spasticity / etiology
  • Muscle Spasticity / therapy*
  • Proteolysis
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / therapy*
  • Voltage-Gated Sodium Channels / metabolism

Substances

  • Voltage-Gated Sodium Channels
  • Calpain