Description
AD represents a critical health problem worldwide [Cold Spring Harb Perpect Med, 2012, 2, 1 – 8] with only few drugs available on the market. Therefore there is a need for development of novel drug(s) to control the AD. Dysfunctional Wnt signaling is associated with Alzheimer`s disease. Increasing evidence suggests that downregulation of Wnt signaling, induced by Aβ, leads to progression of AD. More importantly, persistent activation of Wnt signaling through Wnt ligands, or inhibition of negative regulators of Wnt signaling, such as Dickkopf-1 (DKK-1) and glycogen synthase kinase-3β (GSK-3β) that are hyperactive in the disease state, is able to protect against Aβ toxicity and ameliorate cognitive performance in AD. Wnt increase was shown to compensate action of such AD- factors as Amyloid beta, tau protein and ApoE. It was shown that canonical Wnt signaling potentiator WASP-1 rescues hippocampal synamptic impairments induced by Aβ oligomers (Vargas J.Y. et al., Exp Neurol. 2015 Feb;264:14-25.). Activation of canonical Wnt signaling is involved in the process of Alzheimer's disease not only on the level of competing with amyolid beta, but also on the level of gene regulation. Activation of the Wnt pathway by overexpression of the agonist Wnt3a or β-catenin or by inhibition of glycogen kinase synthase-3 in N2a cells resulted in a reduction in Aβ levels and in the activity and expression of BACE1 (β-APP cleaving enzyme). (Parr et al. FASEB J. 2015; 29: 623-635). In an excellent review Inestrosa et al. [J Mol Cell Biol. 2014; 6: 64-74] focused on the roles of Wnt signaling in synaptic development and function, as well as its neuroprotective effect in AD. Margaret et al. [J Biol Chem. 2008; 283: 9359-9368] . Aβ. Together, this suggests that Wnt signaling might be a potential therapeutic target of AD.