GSK-3 and Wnt signaling in neurogenesis and bipolar disorder

The Wnt signaling pathway is critical for development of the mammalian central nervous system and regulates diverse processes throughout adulthood, including adult neurogenesis. Glycogen Synthase Kinase-3 (GSK-3) antagonizes the Wnt pathway and therefore also plays a central role in neural developme...

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Main Authors: Alexander J Valvezan, Peter S Klein
Format: Article
Language:English
Published: Frontiers Media S.A. 2012-01-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00001/full
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author Alexander J Valvezan
Peter S Klein
Peter S Klein
author_facet Alexander J Valvezan
Peter S Klein
Peter S Klein
author_sort Alexander J Valvezan
collection DOAJ
description The Wnt signaling pathway is critical for development of the mammalian central nervous system and regulates diverse processes throughout adulthood, including adult neurogenesis. Glycogen Synthase Kinase-3 (GSK-3) antagonizes the Wnt pathway and therefore also plays a central role in neural development and adult neurogenesis. As lithium, the first line of therapy for bipolar disorder (BPD), activates Wnt signaling by inhibiting GSK-3, much attention has focused on GSK-3 and Wnt signaling in the therapeutic response to lithium. However, GSK-3 also regulates other critical signaling pathways, including growth factor/neurotrophin signaling downstream of Akt. Here we will review the roles of GSK-3 in CNS development and adult neurogenesis, with a focus on the Wnt pathway. We will also discuss the validation of GSK-3 as the relevant target of lithium and the mechanisms downstream of GSK-3 that influence mammalian behavior.
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spelling doaj.art-817c761f676f4d4fb00f4f2a024cc24e2022-12-22T03:32:05ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992012-01-01510.3389/fnmol.2012.0000117824GSK-3 and Wnt signaling in neurogenesis and bipolar disorderAlexander J Valvezan0Peter S Klein1Peter S Klein2University of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineThe Wnt signaling pathway is critical for development of the mammalian central nervous system and regulates diverse processes throughout adulthood, including adult neurogenesis. Glycogen Synthase Kinase-3 (GSK-3) antagonizes the Wnt pathway and therefore also plays a central role in neural development and adult neurogenesis. As lithium, the first line of therapy for bipolar disorder (BPD), activates Wnt signaling by inhibiting GSK-3, much attention has focused on GSK-3 and Wnt signaling in the therapeutic response to lithium. However, GSK-3 also regulates other critical signaling pathways, including growth factor/neurotrophin signaling downstream of Akt. Here we will review the roles of GSK-3 in CNS development and adult neurogenesis, with a focus on the Wnt pathway. We will also discuss the validation of GSK-3 as the relevant target of lithium and the mechanisms downstream of GSK-3 that influence mammalian behavior.http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00001/fullBehaviorBipolar DisorderLithiumNeurogenesisdevelopmentWnt
spellingShingle Alexander J Valvezan
Peter S Klein
Peter S Klein
GSK-3 and Wnt signaling in neurogenesis and bipolar disorder
Frontiers in Molecular Neuroscience
Behavior
Bipolar Disorder
Lithium
Neurogenesis
development
Wnt
title GSK-3 and Wnt signaling in neurogenesis and bipolar disorder
title_full GSK-3 and Wnt signaling in neurogenesis and bipolar disorder
title_fullStr GSK-3 and Wnt signaling in neurogenesis and bipolar disorder
title_full_unstemmed GSK-3 and Wnt signaling in neurogenesis and bipolar disorder
title_short GSK-3 and Wnt signaling in neurogenesis and bipolar disorder
title_sort gsk 3 and wnt signaling in neurogenesis and bipolar disorder
topic Behavior
Bipolar Disorder
Lithium
Neurogenesis
development
Wnt
url http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00001/full
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