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Int J Physiol Pathophysiol Pharmacol 2012;4(3):140-148
Review Article
The role of glycogen synthase kinase-3 signaling in neurodevelopment and fragile X
syndrome
Samantha Portis, Brian Giunta, Demian Obregon, Jun Tan
Rashid Laboratory for Developmental Neurobiology, Department of Psychiatry and Behavioral Neurosciences, Morsani College of
Medicine, University of South Florida, 3515 E. Fletcher Ave, Tampa, FL 33612; Neuroimmunology Laboratory, Department of Psychiatry
and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612
Received August 17, 2012; Accepted September 5, 2012; Epub September 20, 2012; Published September 30, 2012
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. (IJPPP1208005).
Keywords: Glycogen synthase kinase, fragile X, neuroinflammation, trinucucleotide repeat, microglia, lithium, flavonoids
Address all correspondence to:
Dr. Jun Tan
Rashid Laboratory for Developmental Neurobiology
Silver Child Development Center
Department of Psychiatry and Behavioral Neurosciences
Morsani College of Medicine
University of South Florida
Tampa, Florida, 33613, USA.
Tel: 813-974-9326; Fax: 813-974-1130
E-mail: jtan@health.usf.edu
Review Article
The role of glycogen synthase kinase-3 signaling in neurodevelopment and fragile X
syndrome
Samantha Portis, Brian Giunta, Demian Obregon, Jun Tan
Rashid Laboratory for Developmental Neurobiology, Department of Psychiatry and Behavioral Neurosciences, Morsani College of
Medicine, University of South Florida, 3515 E. Fletcher Ave, Tampa, FL 33612; Neuroimmunology Laboratory, Department of Psychiatry
and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612
Received August 17, 2012; Accepted September 5, 2012; Epub September 20, 2012; Published September 30, 2012
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. (IJPPP1208005).
Keywords: Glycogen synthase kinase, fragile X, neuroinflammation, trinucucleotide repeat, microglia, lithium, flavonoids
Address all correspondence to:
Dr. Jun Tan
Rashid Laboratory for Developmental Neurobiology
Silver Child Development Center
Department of Psychiatry and Behavioral Neurosciences
Morsani College of Medicine
University of South Florida
Tampa, Florida, 33613, USA.
Tel: 813-974-9326; Fax: 813-974-1130
E-mail: jtan@health.usf.edu
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