The role of WNT signaling in neuroprotection

The Wnt signaling pathway has a role in several cellular processes, including cellular communication, embryonic development and cancer. Recent studies show that the Wnt pathway also has an important role in some aspects of neuronal circuit development, such as neuronal migration, synaptic differentiation, mature synapse modulation and synaptic plasticity. Wnt signaling begins during neural development and is crucial for long-term potentiation in the adult brain. The Wnt pathway may have potential in the prevention of neurodegenerative diseases that involve synaptic impairment. Several years ago our laboratory found a relationship between the loss of Wnt signaling and amyloid-β-peptide (Aβ) neurotoxicity, which is involved in Alzheimer's disease (AD). The activation of the Wnt signaling cascade prevents Aβ-dependent cytotoxic effects. We proposed that β-catenin-dependent Wnt ligands have a role in the modulation of presynaptic processes such as neurotransmitter release, β-catenin- independent Wnt signaling controls the postsynaptic site, increasing the incorporation of PSD-95 and glutamatergic receptors in the postsynaptic region. This could prevent the effects of Aβ exposure at the post-synaptic level. The study of the Wnt pathway is a promising approach in the search for possible targets to fight the deleterious effects of neurodegenerative conditions such as AD.