ArticleNeuropsychopharmacology reports2022
Tubulin/microtubules as novel clozapine targets.
Article in Neuropsychopharmacology reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Hyperdynamic microtubule-based structural changes in Monocyte-Derived-Neuronal-like cells from patients with schizophrenia.Schizophrenia (Heidelberg, Germany) · 2026Article
- Structural alteration of neurons in schizophrenia and its relation with auditory hallucination.European psychiatry : the journal of the Association of European Psychiatrists · 2026Article
- Tubulin/microtubules as novel clozapine targets.Neuropsychopharmacology reports · 2022Article
- The microtubule cytoskeleton: An old validated target for novel therapeutic drugs.Frontiers in pharmacology · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimClozapine is currently the only effective drug for treatment-resistant schizophrenia; nonetheless, its pharmacological mechanism remains unclear, and its administration is limited because of severe adverse effects. 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.
methodsFirst, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine-binding proteins in extracts from the cerebra of 7-week-old ICR mice were isolated and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/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.
resultsAlpha and β tubulins were the most abundant clozapine-binding proteins. We also found that clozapine directly binds with α and β tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells.
conclusionThese results suggest that α and β tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.
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