Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 5, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2012.00001
Keywords
Wnt; GSK-3; neurogenesis; lithium; bipolar disorder; behavior; development; psychiatric
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Funding
- NIH [1RO1MH58324, 1R01HL110806]
- Training Program in Hematopoiesis [T32 DK07780]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL110806] Funding Source: NIH RePORTER
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The canonical 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 canonical Wnt pathway and therefore also plays a central role in neural development and adult neurogenesis. Lithium, the first line of therapy for bipolar disorder, inhibits GSK-3, activates Wnt signaling and stimulates adult neurogenesis, which may be important for its therapeutic effects. GSK-3 also regulates other critical signaling pathways which may contribute to the therapeutic effects of lithium, 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 canonical 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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