Abstract
Microtubules, one of the major components of the cytoskeleton, play important roles as pathways for neuronal transport of cellular traffic. The loss of structural stability of microtubules causes detrimental effects on neurons and may contribute to several neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, etc. The triazolopyrimidine class compound cevipabulin is a synthetic microtubule-stabilizing agent that has recently emerged as a drug for the treatment of Alzheimer’s disease. However, the mechanism of microtubule stabilization by cevipabulin has not yet been revealed. Here, we explored the effect of cevipabulin on stabilizing microtubules polymerized from purified tubulins in vitro. We observed the effects of the concentration of microtubule-stabilizing drugs, incubation time, and modification of the cevipabulin structure on the stabilization of microtubules in comparison to those of the most commonly used anticancer drug, paclitaxel. This study will provide insight into the action of cevipabulin in the treatment of neurodegenerative diseases.
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Acknowledgements
This work was financially supported by the Robot Technology Research and Development Project from New Energy and Industrial Technology Development Organization (NEDO), Japan, Grant-in-Aid for Scientific Research on Innovative Areas “Molecular Engine” (JP18H05423 and JP18H03673) and Grant-in-Aid for Young Scientists (A) to AK from the Japan Society for the Promotion of Science (JSPS).
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Nasrin, S.R., Ishihara, T., Kabir, A.M.R. et al. Comparison of microtubules stabilized with the anticancer drugs cevipabulin and paclitaxel. Polym J 52, 969–976 (2020). https://doi.org/10.1038/s41428-020-0334-9
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DOI: https://doi.org/10.1038/s41428-020-0334-9