NeuralCipher Research overview
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Non-canonical Wnt signaling pathways, particularly the Planar Cell Polarity (Wnt/PCP) and Wnt/Ca²⁺ branches, play critical roles in regulating neural development and maintaining cellular homeostasis within the nervous system. This review provides a comprehensive evaluation of the molecular and cellular functions of these pathways, with a focus on their involvement in cytoskeletal dynamics, cellular polarity, and calcium signaling. Non-canonical Wnt signaling is essential for key neurodevelopmental processes, including neural tube closure, neuronal migration, axon guidance, and synaptic plasticity, while its dysregulation contributes to the pathogenesis of both neurodevelopmental and neurodegenerative disorders such as autism spectrum disorder, spina bifida, Alzheimer's disease, and Parkinson's disease. Particular emphasis is placed on the role of Dishevelled (DVL) as a shared intracellular signaling mediator across canonical and non-canonical Wnt pathways, as well as on the context-dependent activation of downstream effectors including Rho GTPases, protein kinase C (PKC), calcium/calmodulin-dependent kinase II (CaMKII), and nuclear factor of activated T-cells (NFAT). In addition, emerging experimental platforms, including CRISPR/Cas9 gene editing and human brain organoids, are highlighted for their utility in dissecting pathway-specific mechanisms and advancing translational applications. Overall, this review underscores the importance of non-canonical Wnt signaling as a dynamic and context-dependent regulatory network and discusses its potential as a target for precision-based therapeutic strategies in neurological disorders.
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