The role of glycogen synthase kinase-3 signaling in neurodevelopment and fragile X syndrome.

Abstract

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.

• Authors: Samantha Portis, Brian Giunta, Demian Obregon, Jun Tan
• Journal: International journal of physiology, pathophysiology and pharmacology (Int J Physiol Pathophysiol Pharmacol) Vol. 4 Issue 3 Pg. 140-8 ( 2012) ISSN: 1944-8171 [Electronic] United States
• PMID: 23071871 (Publication Type: Journal Article)