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The essential role of inositol synthesis in proliferation is underscored by the findings that exogenous inositol was dispensable for proliferation, and inhibition of inositol synthesis decreased proliferation. Interestingly, the inhibition of inositol synthesis by knocking down <jats:italic><jats:styled-content style=\"fixed-case\">INO<\/jats:styled-content>1<\/jats:italic>, which encodes inositol\u20103\u2010phosphate synthase, the rate\u2010limiting enzyme of inositol synthesis, led to the inactivation of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b1 by increasing the inhibitory phosphorylation of this kinase. Similarly, the mood stabilizer valproic acid effected transient decreases in intracellular inositol, leading to inactivation of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b1. As <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103 inhibition has been proposed as a likely therapeutic mechanism of action, the finding that inhibition of inositol synthesis results in the inactivation of <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b1 suggests a unifying hypothesis for mechanism of mood\u2010stabilizing drugs.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12978-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Inositol is an essential metabolite that serves as a precursor for inositol lipids and inositol phosphates. We report that inhibition of the rate\u2010limiting enzyme of inositol synthesis leads to the inactivation of glycogen synthase kinase (GSK) 3\u03b1 by increasing inhibitory phosphorylation of this kinase. These findings have implications for the therapeutic mechanisms of mood stabilizers and suggest that inositol synthesis and GSK 3\u03b1 activity are intrinsically related.<\/jats:p>","DOI":"10.1111\/jnc.12978","type":"journal-article","created":{"date-parts":[[2014,10,27]],"date-time":"2014-10-27T02:09:09Z","timestamp":1414375749000},"page":"273-283","source":"Crossref","is-referenced-by-count":19,"title":["Inositol synthesis regulates the activation of <scp>GSK<\/scp>\u20103\u03b1 in neuronal cells"],"prefix":"10.1111","volume":"133","author":[{"given":"Cunqi","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Wayne State University Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam L.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Wayne State University Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9888(199704)32:4<395::AID-JMS487>3.0.CO;2-#"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio233267a0"},{"key":"e_1_2_7_4_1","first-page":"466","volume-title":"Inositol and Pyrroloquinoline Quinone. 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