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By comparing the binding proteins of clozapine and its derivative olanzapine, which is safer but less effective than clozapine, we attempted to clarify the mechanism of action specific to clozapine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine\u2010binding proteins in extracts from the cerebra of 7\u2010week\u2010old ICR mice were isolated and separated by sodium dodecyl sulfate\u2010polyacrylamide gel electrophoresis (SDS\u2010PAGE) and analyzed by liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS) to identify proteins. Second, the effect of clozapine on tubulin polymerization was determined turbidimetrically. Finally, the cellular effects of clozapine were observed in HeLa cells by immunofluorescence microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alpha and \u03b2 tubulins were the most abundant clozapine\u2010binding proteins. We also found that clozapine directly binds with \u03b1 and \u03b2 tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that \u03b1 and \u03b2 tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12221","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T06:45:32Z","timestamp":1640760332000},"page":"32-41","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tubulin\/microtubules as novel clozapine 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