Excess Wnt in neurological disease

Wnt pathways are critical developmental signaling cascades that are conserved across multicellular life. A clear role for Wnt signaling in proper neural development has been well-established, yet less is known about its sustained expression and signaling in the mature nervous system. The precise role for Wnt pathways, canonical or otherwise, and individual Wnt components (ligands, receptors, transducers, effectors, and regulators) in the mature brain are poorly understood. However, genetic evidence implicating Wnt-related components in both neurodevelopmental and neurodegenerative disorders suggests that fine-tuned regulation of Wnt signaling is required for proper nervous system development and long-term homeostasis. Much has been documented about down-regulated Wnt signaling and its association with neurological conditions. Hence, the focus of this review is to consolidate and highlight the evidence for up-regulated Wnt transcription and/or signaling in neurodevelopmental and neurodegenerative disorders with a brief discussion on the role of deregulated Wnt in cancer. Finally, we touch upon the therapeutic prospect of Wnt inhibition in the nervous system.