Dysregulation of GSK-3 activity is believed to play a key role in the pathogenesis of CNS disorders. GSK-3 and its downstream pathways were shown to be tightly linked with signaling pathways regulating synaptic modulation, neuroprotection and neuroplasticity. Of particular relevance to neurodegenarative disorders, GSK-3 binds and / or phosphoryltes tau, presenilin-1, and collapsin response mediator protein, CRMP2, proteins that are implicated in the etiology of Alzheimer’s disease. Specifically, GSK-3 phosphorylates tau in most serine and threonine residues which are hyperphosphorylated in PHF (paired helical filament) in brains of Alzheimer’s patients. Subsequently, the phosphorylation of CRMP2 by GSK-3 affects neuroplasticity and axon grwoth. In addition, GSK-3 activity contributes to the production of Aβ peptide, the principal protein component of amyloid plaques, the hallmark of Alzheimer’s disease pathology. Furthermore, recent work suggested a mechanistic link between amyloid signaling and tauopathy via activation of GSK-3.