**1. Introduction**

Wnts compromise a large family of secreted glycoproteins that have shown to be part of the signaling molecules that regulate several aspects of development such as axis formation and midbrain development [1, 2]. In mammals at least 19 Wnt members have been found. The interaction of a Wnt protein with members of the Frizzled (Fz) family of seven-pass trans‐ membrane cell-surface receptors triggers the activation of the Wnt signaling pathway [3-5]. In human and mice, 10 members of the Fz family have been identified. In addition, receptor-like tyrosine kinase (Ryk) and receptor tyrosine kinase-like orphan receptor (Ror2) have been identified as alternative Wnt receptors [6-8]. Different Wnt signaling cascades are activated downstream the Wnt receptors, identified as Wnt/β-catenin or canonical pathway, and βcatenin-independent or non-canonical pathways. The canonical pathway involves the tran‐ scription of Wnt target genes, while activation of non-canonical Wnt pathways may induce either an increase in intracellular calcium concentration or activation of the c-Jun-N-terminal kinase (JNK) cascade [3, 9, 10].

The Wnt pathway participates in the development of the central nervous system (CNS) and growing evidence indicate that Wnts also regulates the function of the adult nervous system [11, 12]. In fact, most of the key components including Wnts and Fz receptors are expressed in the adult brain [13, 14]. Wnt ligands have shown to regulate synaptic assembly as well synaptic plasticity and neurotransmission [15-20], and more recently it has also been involved in the adult neurogenesis [21-25].

Deregulation of the Wnt signaling has been associated to several pathologies, been cancer the most widely documented [26-28]. More recently, altered Wnt signaling have been related to mental disorders, mood disorders and neurodegenerative diseases [12, 29-32].

© 2013 Inestrosa and Varela-Nallar; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Inestrosa and Varela-Nallar; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In the first part of this chapter we will address what is currently known about the signaling cascades of canonical and non-canonical pathways. Then, we will review recent findings from our and other labs on the specific effects of different Wnt ligands on the structure of pre- and postsynaptic regions and on glutamatergic neurotransmission in hippocampal neurons. The synaptic role of some Fz receptors will also be reviewed. Finally, the neuroprotective effect of the Wnt signaling activation will be discussed mainly focused on the protection against the toxicity of Aβ-peptide aggregates associated to the pathogene‐ sis of Alzheimer's disease.
