Expression of Wnt5a and its receptor Fzd2 is changed in the spinal cord of adult amyotrophic lateral sclerosis transgenic mice.

Wnt5a, a member of the Wnt gene family, encodes a cysteine-rich growth factor involved in signal transduction during growth and differentiation. The Fzd2 gene codes for a cell membrane receptor called Frizzled-2 have a structure similar to G protein coupled receptors. The extracellular N-terminal of the Fzd2 receptor has a cysteine-rich domain (CRD) that binds Wnt ligands and thus primes the Wnt signal pathway. Downregulation of the Wnt signal pathway occurs in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). However, little is known about Wnt5a/Fzd2 signaling in mammalian nerve cells, and it is not clear whether Wnt5a or Fzd2 functioning are changed in ALS. The influence of Wnt5a and Fzd2 signal transduction pathway on ALS was investigated in adult SOD1(G93A) transgenic mice. Changes in Wnt5a and Fzd2 expression in the spinal cord of SOD1(G93A) transgenic mice (ALS), SOD1(G93A) transfected NSC-34 cells, and primary cultures of astrocytes from SOD1(G93A) transgenic mice were detected by immunofluorescent staining, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The results provide further insight into the role of Wnt5a and Fzd2 in the pathogenesis of ALS transgenic mice, which provides evidence that should help in the search for treatments of ALS.