Role of Wnt signaling in synaptic plasticity and memory

Ever since their discoveries, the Wnt pathways have been consistently associated with key features of cellular development, including metabolism, structure and cell fate. The three known pathways (the canonical Wnt/β-catenin and the two non-canonical Wnt/Ca⁺⁺ and Wnt/JNK/PCP pathways) participate in complex networks of interaction with a wide range of regulators of cell function, such as GSK-3β, AKT, PKC and mTOR, among others. These proteins are known to be involved in the formation and maintenance of memory. Currently, studies with Wnt and memory have shown that the canonical and non-canonical pathways play key roles in different processes associated with memory. So, in this review we briefly summarize the different roles that Wnt signaling can play in neurons and in memory, as well as in Alzheimer's disease, focusing towards animal studies. We start with the molecular characterization of the family and its receptors, as well as the most commonly used drugs for pharmacological manipulations. Next, we describe its role in synaptic plasticity and memory, and how the regulations of these pathways affect crucial features of neuronal function. Furthermore, we succinctly present the current knowledge on how the Wnt pathways are implicated in Alzheimer's disease, and how studies are seeing them as a potential candidate for effective treatments. Lastly, we point toward challenges of Wnt research, and how knowledge on these pathways can lead towards a better understanding of neurobiological and pathological processes.