The mechanism of the WNT5A and FZD4 receptor mediated WNT/β-catenin pathway in the degeneration of ALS spinal cord motor neurons

Biochem Biophys Res Commun. 2022 Jun 18:609:23-30. doi: 10.1016/j.bbrc.2022.03.126. Epub 2022 Apr 1.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with unknown etiology, characterized by motor neuron degeneration, and there is no highly effective treatment. The canonical WNT/β-catenin signaling pathway has a critical role in the physiological and pathophysiological processes of the central nervous system. In this study, we investigated the regulatory mechanism of the WNT/β-catenin signaling pathway from the perspective of ligand-receptor binding and its relationship with the degeneration of ALS motor neurons. We used hSOD1-G93A mutant ALS transgenic mice and hSOD1-G93A mutant NSC34 cells combined with morphological and molecular biology techniques to determine the role of the WNT/β-catenin pathway in ALS. Our findings demonstrated that WNT5A regulates the WNT/β-catenin signaling pathway by binding to the FZD4 receptor in the pathogenesis of ALS and affects the proliferation and apoptosis of ALS motor neurons. Therefore, these findings may lead to the development of novel therapies to support the survival of ALS motor neurons.

Keywords: Active-β-catenin; Amyotrophic lateral sclerosis; FZD4; NSC34 cells; Transgenic mice; WNT5A.

MeSH terms

  • Amyotrophic Lateral Sclerosis* / metabolism
  • Animals
  • Disease Models, Animal
  • Frizzled Receptors / metabolism*
  • Mice
  • Mice, Transgenic
  • Motor Neurons / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Spinal Cord / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1 / metabolism
  • Wnt Signaling Pathway
  • Wnt-5a Protein / metabolism*
  • beta Catenin / metabolism

Substances

  • Frizzled Receptors
  • Fzd4 protein, mouse
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • beta Catenin
  • Superoxide Dismutase
  • Superoxide Dismutase-1