{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T12:56:12Z","timestamp":1781268972544,"version":"3.54.1"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytoskeleton"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neurodegenerative diseases have largely been defined by the accumulation of misfolded and aggregated proteins, while cytoskeletal disruption has typically been treated as a secondary consequence of pathology. Here, we argue that tubulin and microtubules are active determinants of whether disease\u2010linked proteins remain functionally engaged or enter pathological assembly pathways. Recent evidence that tubulin redirects Tau:\u03b1\u2010synuclein condensates away from oligomerization and amyloid formation toward physiological, microtubule\u2010association competent states supports this view. On this basis, we propose that loss of productive protein\u2010microtubule engagement shifts intracellular binding equilibria toward disengaged protein populations, available to access pathological homo\u2010 and heterotypic interactions. These macromolecular aggregates may then further disrupt microtubule organization, exacerbating cytoskeletal failure and accelerating disease progression. This view also offers an explanation for mixed pathologies, as release from one function\u2010related interaction network expands access to several pathogenic ones. We further consider the implications of this model for therapy and biomarker development, positioning the tubulin\/microtubule system as both a targetable regulator of proteostatic fate and a biologically informative readout of early pathology. In this perspective, tubulin state is not a passive marker of damage but a determinant of neurodegenerative protein behavior.<\/jats:p>","DOI":"10.1002\/cm.70162","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:57:39Z","timestamp":1781265459000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tubulin State Determines Proteopathic Fate"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-0015","authenticated-orcid":false,"given":"Lathan","family":"Lucas","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"My Diem","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine C.","family":"Ferreon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Chris M.","family":"Ferreon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"issue":"3","key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.neuron.2013.12.018","article-title":"Axonal Transport of TDP\u201043 mRNA Granules Is Impaired by ALS\u2010Causing Mutations","volume":"81","author":"Alami N. 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