Expression of the axon-guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis

Eur J Neurosci. 2019 Jun;49(11):1529-1543. doi: 10.1111/ejn.14326. Epub 2019 Jan 16.


Amyotrophic Lateral Sclerosis (ALS) is a degenerative motor neuron disorder. It is supposed that ALS is at least in part an axonopathy. Neuropilin 1 is an important receptor of the axon repellent Semaphorin 3A and a co-receptor of vascular endothelial growth factor. It is probably involved in neuronal and axonal de-/regeneration and might be of high relevance for ALS pathogenesis and/or disease progression. To elucidate whether the expression of either Neuropilin1 or Semaphorin3A is altered in ALS we investigated these proteins in human brain, spinal cord and muscle tissue of ALS-patients and controls as well as transgenic SOD1G93A and control mice. Neuropilin1 and Semaphorin3A gene and protein expression were assessed by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. Groups were compared using either Student t-test or Mann-Whitney U test. We observed a consistent increase of Neuropilin1 expression in the spinal cord and decrease of Neuropilin1 and Semaphorin3A in muscle tissue of transgenic SOD1G93A mice at the mRNA and protein level. Previous studies have shown that damage of neurons physiologically causes Neuropilin1 and Semaphorin3A increase in the central nervous system and decrease in the peripheral nervous system. Our results indicate that this also occurs in ALS. Pharmacological modulation of expression and function of axon repellents could be a promising future therapeutic option in ALS.

Keywords: amyotrophic lateral sclerosis; axon guidance molecules; semaphorin 3A; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Muscle, Skeletal / metabolism*
  • Neuropilin-1 / metabolism*
  • Semaphorin-3A / metabolism
  • Spinal Cord / metabolism*


  • Semaphorin-3A
  • Neuropilin-1

Associated data

  • GENBANK/NM_003873.5
  • GENBANK/NM_021130.4
  • GENBANK/NM_008737.2
  • GENBANK/NM_009152.4
  • GENBANK/NM_008907.1
  • GENBANK/NM_013556.2