Fragile X syndrome (FXS), one of the most common genetic causes of
autism, results from a loss of
fragile X mental retardation protein (FMRP) expression. At the molecular level, abnormal neurodevelopment is thought to result from dysregulated
protein synthesis of key neural synaptic
proteins, however recent evidence suggests broader roles for this
protein including
glutamate signaling, memory, and regulation of the critical
serine/
threonine regulatory
kinase, glycogen synthase kinase-3 (GSK-3). In this review, genetic and molecular features of FXS are detailed in the context of FXS neuropathology. Additionally, potential mechanisms by which FMRP silencing impacts
GSK-3 and GSK-3-associated signaling pathways are discussed. As
GSK-3 signaling represents a central regulatory node for critical neurodevelopmental pathways, understanding how FXS results from FMRP-mediated
GSK-3 dysregulation may provide novel therapeutic targets for disease-modifying interventions for FXS and related ASDs.