Drug Discovery for Schizophrenia
CHAPTER 8: GSK3 Networks in Schizophrenia
Published:28 Apr 2015
Special Collection: 2015 ebook collection , 2011-2015 industrial and pharmaceutical chemistry subject collectionSeries: Drug Discovery
Glycogen synthase kinase (GSK)-3, a ubiquitous serine/threonine kinase, was first identified in the late 1970s as a key enzyme in glucose metabolism. Its association with a multitude of neuronal events and signaling processes has emerged ever since and ample evidence now converges on a prominent role of this conserved kinase in neuropsychiatric disorders such as schizophrenia. First evidence came from the observations that many schizophrenia risk genes directly interact with or are the members of cascades signaling through GSK-3. The fact that both antipsychotics and psychosis-inducing agents influence GSK-3 activity either directly or indirectly position this regulatory enzyme at the crossroads of the pathways that lead to behavioral outcomes and cognitive functions. In this chapter, we describe the major signal transduction cascades regulating GSK-3 activity and the findings of human and animal studies on alteration or deregulation of the GSK-3 signaling partners and networks in schizophrenia. We elaborate on how GSK-3 interaction with its established and putative partners might culminate in behavioral phenotypes. We further speculate how these findings could be exploited to develop novel diagnostics and therapeutic strategies for schizophrenia that target GSK-3 or its interacting molecules.