{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:40Z","timestamp":1785431440184,"version":"3.56.0"},"reference-count":143,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biology at Syracuse University"},{"id":[{"id":"https:\/\/ror.org\/025r5qe02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) and related tauopathies are marked by progressive cognitive decline, synaptic dysfunction, and neuronal loss. The microtubule (MT)-associated protein tau, encoded by the MAPT gene, plays a central role in neurodegenerative pathology. Although the dissociation of hyperphosphorylated tau from MTs and their subsequent aggregation has been extensively studied, the broader landscape of other MT-associated proteins remains largely underexplored. Among these, the end-binding protein (EBP) family, which comprises MT plus-end-tracking proteins, has emerged as a critical regulator of MT dynamics and stability. EBPs modulate MT polymerization, interact with various MT-associated proteins, and influence cytoskeletal organization. Recent studies suggest that pathological tau impairs end-binding protein 3 (EB3) function by limiting its localization to MT plus-ends and inhibiting EB3-mediated MT elongation and stability. In addition, EB1 appears to interfere with tau aggregation in an in vitro study involving biomolecular condensates. Dysregulation of dynamic tau-MT-EBP interactions may result in structural and functional consequences throughout the entire network, potentially increasing MT instability under neurodegenerative conditions. Hence, the tau-MT-EBP network is an emerging mechanistic axis for advancing the understanding of physiological processes, disease pathology, and therapeutic interventions. In this review, we summarize recent advances in understanding the tau-MT-EBP axis and highlight the molecular mechanisms underlying key pathological interactions within this network. Finally, we discuss current therapeutic strategies and future directions for targeting this dynamic axis to mitigate AD and related tauopathies.<\/jats:p>","DOI":"10.3390\/ijms27125467","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"5467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dysregulation of the Tau-Microtubule-End-Binding Protein Axis in Alzheimer\u2019s Disease and Related Tauopathies"],"prefix":"10.3390","volume":"27","author":[{"given":"Mahmudul","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Biology, Syracuse University, Syracuse, NY 13244, USA"},{"name":"Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kholoud","family":"Abd-ElRaouf","sequence":"additional","affiliation":[{"name":"Department of Biology, Syracuse University, Syracuse, NY 13244, USA"},{"name":"Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia R.","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Biology, Syracuse University, Syracuse, NY 13244, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-4484","authenticated-orcid":false,"given":"Chih Hung","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Biology, Syracuse University, Syracuse, NY 13244, USA"},{"name":"Interdisciplinary Neuroscience Program, Syracuse University, Syracuse, NY 13244, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41582-022-00749-z","article-title":"Synaptic Degeneration in Alzheimer Disease","volume":"19","author":"Tzioras","year":"2022","journal-title":"Nat. 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