β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain.
This suggests a general role for β-catenin in synaptic remodeling and stabilization underlying long-term memory in adults, and possible roles for dysfunction in the β-catenin pathway in disorders of memory impairment (e.g.
We report here that: (a) a bioinformatic analysis of 15,476 promoters of the human genome predicted several Wnt target genes, being CaMKIV a very interesting candidate; (b) CaMKIV promoter contains TCF/LEF transcription motifs similar to those present in Wnt target genes; (c) biochemical studies indicate that lithium and the canonical ligand Wnt-3a induce CaMKIV mRNA and protein expression levels in rat hippocampal neurons as well as CaMKIV promoter activity; (d) treatment of hippocampal neurons with Wnt-3a increases the binding of beta-catenin to the CaMKIV promoter: (e) In vivo activation of the Wnt signaling improve spatial memory impairment and restores the expression of CaMKIV in a mice double transgenic model for Alzheimer's disease which shows decreased levels of the kinase.