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In homeostatic microglia, microtubules are nucleated at Golgi outposts, supporting ramified architectures and low inflammatory tone. Upon activation, microglia undergo a switch to a centrosome-nucleated, radial microtubule array, driven in part by cyclin-dependent kinase 1 (Cdk1) and associated with polarized cytokine release, NLRP3 inflammasome engagement, and altered phagocytic behavior. We discuss how key regulators of this transition-including Cdk1, centrosomal \u03b3-tubulin recruitment, Golgi-derived microtubule nucleation, and the kinase MARK4 may constitute druggable nodes to tune microglial reactivity in neuro-degenerative diseases. Finally, we outline experimental priorities for translating microglial microtubules into therapeutic targets.<\/jats:p>","DOI":"10.3389\/fnins.2026.1812417","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:15:37Z","timestamp":1776698137000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting microglia microtubules: cytoskeletal remodeling as a druggable hub in neuroinflammation and neurodegeneration"],"prefix":"10.3389","volume":"20","author":[{"given":"Caterina","family":"Sanchini","sequence":"first","affiliation":[{"name":"Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rosito","sequence":"additional","affiliation":[{"name":"Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia","place":["Rome, Italy"]},{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Department of Pathology & Cell Biology, Columbia University Irving Medical Center","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Di Angelantonio","sequence":"additional","affiliation":[{"name":"Center for Life Nano- & Neuro-Science, Istituto Italiano di Tecnologia","place":["Rome, Italy"]},{"name":"Department of Physiology and Pharmacology, Sapienza University","place":["Rome, Italy"]},{"name":"D-Tails Research srl BC","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"iPSC-derived human microglia-like cells to study neurological diseases","author":"Abud","year":"2017","journal-title":"Neuron 94"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-41891-6","volume-title":"Polarized Microtubule Remodeling Transforms the Morphology of Reactive Microglia and Drives Cytokine Release.","author":"Adrian","year":"2023"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2978","DOI":"10.1038\/s41467-024-46379-5","article-title":"Microtubule damage shapes the acetylation gradient","volume":"15","author":"Andreu-Carb\u00f3","year":"2024","journal-title":"Nat. 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