{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:11:46Z","timestamp":1793052706875,"version":"4.5.0"},"reference-count":260,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271446"],"award-info":[{"award-number":["82271446"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471442"],"award-info":[{"award-number":["82471442"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024BCA003"],"award-info":[{"award-number":["2024BCA003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major Project of Science and Technology Innovation of Hubei Province","award":["82271446"],"award-info":[{"award-number":["82271446"]}]},{"name":"Major Project of Science and Technology Innovation of Hubei Province","award":["82471442"],"award-info":[{"award-number":["82471442"]}]},{"name":"Major Project of Science and Technology Innovation of Hubei Province","award":["2024BCA003"],"award-info":[{"award-number":["2024BCA003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The aggregation of Tau protein into neurofibrillary tangles (NFTs), a hallmark of Alzheimer\u2019s disease (AD), is associated with cognitive decline. Recent studies have revealed that neuronal cytoskeletal instability drives early AD pathogenesis. The physiological interaction between tau and the microtubule (MT) is crucial for maintaining axonal transport and stability. However, aberrant post-translational modifications (PTMs) in the MT binding domain\u2014such as phosphorylation, acetylation and ubiquitination\u2014trigger tau dissociation, causing microtubule collapse, transport deficits, and synaptic dysfunction. MT dysregulation also affects actin\/cofilin-mediated dendritic spine destabilization and causes the hyperplasia of the glial intermediate filament, which exacerbates neuroinflammation and synaptic toxicity. This review systematically explores the functions of neuronal cytoskeletons, deciphers the molecular crosstalk between tau pathology and cytoskeletal remodeling, and proposes multi-target therapeutic strategies to restore cytoskeletal homeostasis, thereby providing novel perspectives for precision interventions in AD<\/jats:p>","DOI":"10.3390\/biom15060831","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:08:31Z","timestamp":1749208111000},"page":"831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Cytoskeletal Proteins and Alzheimer\u2019s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology"],"prefix":"10.3390","volume":"15","author":[{"given":"Gege","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanfeng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2221-5972","authenticated-orcid":false,"given":"Jing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430000, China"},{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Life Sciences, Wuhan University, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). Global Action Plan on the Public Health Response to Dementia 2017\u20132025, World Health Organization. Available online: https:\/\/iris.who.int\/handle\/10665\/259615."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0896-6273(91)90052-2","article-title":"The molecular pathology of Alzheimer\u2019s disease","volume":"6","author":"Selkoe","year":"1991","journal-title":"Neuron"},{"key":"ref_3","first-page":"e933084","article-title":"The Role of Amyloid-Beta and Tau in the Early Pathogenesis of Alzheimer\u2019s Disease","volume":"27","author":"Yin","year":"2021","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_4","unstructured":"(2025, March 26). Comprehensive Review on Alzheimer\u2019s Disease: Causes and Treatment, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/33302541\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa2305032","article-title":"Trial of Solanezumab in Preclinical Alzheimer\u2019s Disease","volume":"389","author":"Sperling","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-med-051022-043645","article-title":"Lessons Learned from Approval of Aducanumab for Alzheimer\u2019s Disease","volume":"75","author":"Heidebrink","year":"2024","journal-title":"Annu. Rev. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41582-020-00454-9","article-title":"Aducanumab and the FDA\u2014Where are we now?","volume":"17","author":"Fillit","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_8","unstructured":"(2025, March 26). Lecanemab in Early Alzheimer\u2019s Disease, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/36449413\/."},{"key":"ref_9","unstructured":"(2025, March 26). Lecanemab: First Approval, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/36856953\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.14283\/jpad.2020.24","article-title":"The Future of Anti-Amyloid Trials","volume":"7","author":"Aisen","year":"2020","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"n156","DOI":"10.1136\/bmj.n156","article-title":"Effect of reductions in amyloid levels on cognitive change in randomized trials: Instrumental variable meta-analysis","volume":"372","author":"Ackley","year":"2021","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","article-title":"Neurodegenerative tauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1001\/jamaneurol.2019.1424","article-title":"Association of Amyloid and Tau with Cognition in Preclinical Alzheimer Disease: A Longitudinal Study","volume":"76","author":"Hanseeuw","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/brain\/aww027","article-title":"Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer\u2019s disease","volume":"139","author":"Ossenkoppele","year":"2016","journal-title":"Brain J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nrd.2017.155","article-title":"Tau-based therapies in neurodegeneration: Opportunities and challenges","volume":"16","author":"Li","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/s41591-025-03494-0","article-title":"Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia","volume":"31","author":"Fernandez","year":"2025","journal-title":"Nat. Med."},{"key":"ref_18","unstructured":"(2025, March 26). Resilience to Autosomal Dominant Alzheimer\u2019s Disease in a Reelin-COLBOS Heterozygous Man, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/37188781\/."},{"key":"ref_19","unstructured":"(2025, March 26). Resistance to Autosomal Dominant Alzheimer\u2019s Disease in an APOE3 Christchurch Homozygote: A Case Report, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/31686034\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1007\/s12035-023-03281-3","article-title":"Phosphomimetics at Ser199\/Ser202\/Thr205 in Tau Impairs Axonal Transport in Rat Hippocampal Neurons","volume":"60","author":"Christensen","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_21","unstructured":"(2025, March 26). Alzheimer\u2019s Disease: Phenotypic Approaches Using Disease Models and the Targeting of Tau Protein, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/32116063\/."},{"key":"ref_22","unstructured":"(2025, March 26). Tau Induces Inflammasome Activation and Microgliosis Through Acetylating NLRP3, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/38488468\/."},{"key":"ref_23","unstructured":"(2025, March 26). Aggregated Tau Activates NLRP3-ASC Inflammasome Exacerbating Exogenously Seeded and Non-Exogenously Seeded Tau Pathology In Vivo, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/30721409\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105973","DOI":"10.1016\/j.phrs.2021.105973","article-title":"Mitophagy enhancers against phosphorylated Tau-induced mitochondrial and synaptic toxicities in Alzheimer disease","volume":"174","author":"Kshirsagar","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1007\/s12035-020-02084-0","article-title":"The Crosstalk Between Pathological Tau Phosphorylation and Mitochondrial Dysfunction as a Key to Understanding and Treating Alzheimer\u2019s Disease","volume":"57","author":"Guha","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Glynn, C., Rodriguez, J.A., and Hyman, B.T. (2024). The structural line between prion and \u201cprion-like\u201d: Insights from prion protein and tau. Curr. Opin. Neurobiol., 86.","DOI":"10.1016\/j.conb.2024.102857"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40478-021-01127-4","article-title":"Alzheimer\u2019s disease brain contains tau fractions with differential prion-like activities","volume":"9","author":"Li","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_28","unstructured":"(2025, March 26). Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-to-Neuron Transmission, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/38327094\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1126\/science.177.4054.1104","article-title":"Microtubule formation in vitro in solutions containing low calcium concentrations","volume":"177","author":"Weisenberg","year":"1972","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Lasso, D.C., Rom\u00e1-Mateo, C., Pallard\u00f3, F.V., and Gonzalez-Cabo, P. (2020). Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders. Cells, 9.","DOI":"10.3390\/cells9020358"},{"key":"ref_31","unstructured":"(2025, March 26). Actin and Actin-Binding Proteins: Masters of Dendritic Spine Formation, Morphology, and Function, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/20717495\/."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jung, M., Kim, D., and Mun, J.Y. (2020). Direct Visualization of Actin Filaments and Actin-Binding Proteins in Neuronal Cells. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.588556"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yuan, A., Rao, M.V., and Nixon, R.A. (2017). Neurofilaments and Neurofilament Proteins in Health and Disease. Cold Spring Harb. Perspect. Biol., 9.","DOI":"10.1101\/cshperspect.a018309"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ding, E.A., and Kumar, S. (2024). Neurofilament Biophysics: From Structure to Biomechanics. Mol. Biol. Cell, 35.","DOI":"10.1091\/mbc.E23-11-0438"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Acosta, D.M., Mancinelli, C., Bracken, C., and Eliezer, D. (2022). Post-translational modifications within tau paired helical filament nucleating motifs perturb microtubule interactions and oligomer formation. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2021.101442"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/0959-4388(95)80073-5","article-title":"Disruption of the cytoskeleton in Alzheimer\u2019s disease","volume":"5","author":"Lee","year":"1995","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00401-017-1707-9","article-title":"Roles of tau protein in health and disease","volume":"133","author":"Guo","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.1073\/pnas.83.13.4913","article-title":"Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology","volume":"83","author":"Iqbal","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1021\/jm301079z","article-title":"Microtubule stabilizing agents as potential treatment for Alzheimer\u2019s disease and related neurodegenerative tauopathies","volume":"55","author":"Ballatore","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1016\/j.febslet.2010.06.014","article-title":"Microtubule destruction induces tau liberation and its subsequent phosphorylation","volume":"584","author":"Miyasaka","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/cercor\/10.10.927","article-title":"Regulation of dendritic spine morphology by the rho family of small GTPases: Antagonistic roles of Rac and Rho","volume":"10","author":"Tashiro","year":"2000","journal-title":"Cereb. Cortex"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.279.5350.509","article-title":"Rho GTPases and the actin cytoskeleton","volume":"279","author":"Hall","year":"1998","journal-title":"Science"},{"key":"ref_43","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":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.conb.2019.01.003","article-title":"Microtubule control of functional architecture in neurons","volume":"57","author":"Kelliher","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrn2631","article-title":"Microtubule assembly, organization and dynamics in axons and dendrites","volume":"10","author":"Conde","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_46","unstructured":"(2025, April 23). Microtubules in Neurons as Information Carriers, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/24266899\/."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/iub.1384","article-title":"Microtubule-associated proteins as direct crosslinkers of actin filaments and microtubules","volume":"67","author":"Mohan","year":"2015","journal-title":"IUBMB Life"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41580-018-0067-1","article-title":"Actin-microtubule crosstalk in cell biology","volume":"20","author":"Dogterom","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.neuron.2015.05.046","article-title":"Building the Neuronal Microtubule Cytoskeleton","volume":"87","author":"Kapitein","year":"2015","journal-title":"Neuron"},{"key":"ref_50","unstructured":"(2025, March 26). Actin Dynamics in Growth Cone Motility and Navigation, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/24164353\/."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3390\/toxics3030322","article-title":"Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy","volume":"3","author":"Nicolini","year":"2015","journal-title":"Toxics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.bbadis.2006.04.002","article-title":"Axonal transport and neurodegenerative disease","volume":"1762","author":"Holzbaur","year":"2006","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.tibs.2015.08.003","article-title":"Regulation of Axonal Transport by Protein Kinases","volume":"40","author":"Gibbs","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1146\/annurev.cellbio.13.1.83","article-title":"Microtubule polymerization dynamics","volume":"13","author":"Desai","year":"1997","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R516","DOI":"10.1016\/j.cub.2006.06.044","article-title":"Microtubule dynamic instability","volume":"16","author":"Burbank","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Goodson, H.V., and Jonasson, E.M. (2018). Microtubules and Microtubule-Associated Proteins. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a022608"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0092-8674(86)90318-1","article-title":"Beyond self-assembly: From microtubules to morphogenesis","volume":"45","author":"Kirschner","year":"1986","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1126\/science.1084938","article-title":"Microtubule asymmetry","volume":"300","author":"Gundersen","year":"2003","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1073\/pnas.70.3.765","article-title":"Microtubule assembly in the absence of added nucleotides","volume":"70","author":"Shelanski","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nrm3853","article-title":"Bidirectional cargo transport: Moving beyond tug of war","volume":"15","author":"Hancock","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.tins.2014.08.004","article-title":"Lost after translation: Missorting of Tau protein and consequences for Alzheimer disease","volume":"37","author":"Zempel","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_62","unstructured":"(2025, March 26). Multiple Isoforms of Human Microtubule-Associated Protein Tau: Sequences and Localization in Neurofibrillary Tangles of Alzheimer\u2019s Disease, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/2484340\/."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"921","DOI":"10.3233\/JAD-2012-112057","article-title":"Tau isoform with three microtubule binding domains is a marker of new axons generated from the subgranular zone in the hippocampal dentate gyrus: Implications for Alzheimer\u2019s disease","volume":"29","author":"Teixeira","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_64","unstructured":"(2025, March 26). Tau Isoform Regulation is Region- and Cell-Specific in Mouse Brain, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/18925637\/."},{"key":"ref_65","unstructured":"(2025, March 26). Tau in Physiology and Pathology, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/26631930\/."},{"key":"ref_66","unstructured":"(2025, March 26). Tau Protein and Adult Hippocampal Neurogenesis, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/22787440\/."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Avila, J., Jim\u00e9nez, J.S., Sayas, C.L., Bol\u00f3s, M., Zabala, J.C., Rivas, G., and Hern\u00e1ndez, F. (2016). Tau Structures. Front. Aging Neurosci., 8.","DOI":"10.3389\/fnagi.2016.00262"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12230","DOI":"10.1074\/jbc.M607159200","article-title":"The \u201cjaws\u201d of the tau-microtubule interaction","volume":"282","author":"Mukrasch","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1021\/bi061920i","article-title":"NMR investigation of the interaction between the neuronal protein tau and the microtubules","volume":"46","author":"Sillen","year":"2007","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7501","DOI":"10.1073\/pnas.1504081112","article-title":"Tau stabilizes microtubules by binding at the interface between tubulin heterodimers","volume":"112","author":"Kadavath","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9511","DOI":"10.1021\/bi00198a017","article-title":"Domains of tau protein and interactions with microtubules","volume":"33","author":"Gustke","year":"1994","journal-title":"Biochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1091\/mbc.e04-01-0062","article-title":"Modulation of microtubule dynamics by tau in living cells: Implications for development and neurodegeneration","volume":"15","author":"Bunker","year":"2004","journal-title":"Mol. Biol. Cell."},{"key":"ref_73","unstructured":"(2025, March 26). FTDP-17 Mutations Compromise the Ability of Tau to Regulate Microtubule Dynamics in Cells, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/16495230\/."},{"key":"ref_74","first-page":"2810","article-title":"Molecular mechanisms of Tau binding to microtubules and its role in microtubule dynamics in live cells","volume":"126","author":"Breuzard","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"101782","DOI":"10.1016\/j.isci.2020.101782","article-title":"Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends","volume":"23","author":"Castle","year":"2020","journal-title":"iScience"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1126\/science.1152993","article-title":"Differential regulation of dynein and kinesin motor proteins by tau","volume":"319","author":"Dixit","year":"2008","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/s41556-019-0374-6","article-title":"Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes","volume":"21","author":"Siahaan","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_78","unstructured":"(2025, March 26). Microtubules Gate Tau Condensation to Spatially Regulate Microtubule Functions, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/31481790\/."},{"key":"ref_79","unstructured":"(2025, March 26). Overexpression of Tau Protein Inhibits Kinesin-Dependent Trafficking of Vesicles, Mitochondria, and Endoplasmic Reticulum: Implications for Alzheimer\u2019s Disease, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/9813097\/."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1073\/pnas.0607919104","article-title":"Multiple-motor based transport and its regulation by Tau","volume":"104","author":"Vershinin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","unstructured":"(2025, March 26). Dendritic Function of Tau Mediates Amyloid-Beta Toxicity in Alzheimer\u2019s Disease Mouse Models, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/20655099\/."},{"key":"ref_82","unstructured":"(2025, March 26). Activity-Dependent Tau Protein Translocation to Excitatory Synapse is Disrupted by Exposure to Amyloid-Beta Oligomers, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/24760868\/."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.neuint.2011.12.013","article-title":"Tau protein is involved in morphological plasticity in hippocampal neurons in response to BDNF","volume":"60","author":"Chen","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_84","unstructured":"(2025, March 26). Novel Function of Tau in Regulating the Effects of External Stimuli on Adult Hippocampal Neurogenesis, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/27198172\/."},{"key":"ref_85","unstructured":"(2025, March 26). Interaction Between the Guanylate Kinase Domain of PSD-95 and the Proline-Rich Region and Microtubule Binding Repeats 2 and 3 of Tau, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/33794133\/."},{"key":"ref_86","unstructured":"(2025, March 26). Interaction of Endogenous Tau Protein with Synaptic Proteins Is Regulated by N-Methyl-D-Aspartate Receptor-Dependent Tau Phosphorylation, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/22833681\/."},{"key":"ref_87","unstructured":"(2025, March 27). The MAP1 Family of Microtubule-Associated Proteins, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/16938900\/."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1073\/pnas.82.16.5404","article-title":"Microtubule-associated protein 1B: Identification of a major component of the neuronal cytoskeleton","volume":"82","author":"Bloom","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","unstructured":"(2025, March 27). Microtubule-Associated Proteins (MAPs): A Monoclonal Antibody to MAP 1 Decorates Microtubules In Vitro but Stains Stress Fibers and not Microtubules In Vivo, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/3883359\/."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1083\/jcb.143.3.695","article-title":"Novel features of the light chain of microtubule-associated protein MAP1B: Microtubule stabilization, self interaction, actin filament binding, and regulation by the heavy chain","volume":"143","author":"Wiche","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1074\/jbc.M408984200","article-title":"Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family","volume":"280","author":"Simader","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1097\/00001756-199804200-00015","article-title":"Differential interactions of MAP2, tau and MAP5 during axogenesis in culture","volume":"9","author":"Kwei","year":"1998","journal-title":"Neuroreport"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"9565","DOI":"10.1523\/JNEUROSCI.17-24-09565.1997","article-title":"Isoform specificity in the relationship of actin to dendritic spines","volume":"17","author":"Kaech","year":"1997","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/jnc.12313","article-title":"Actin filaments and microtubules in dendritic spines","volume":"126","author":"Shirao","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_95","unstructured":"(2025, March 27). Microtubule-Associated Protein 2 Mediates Induction of Long-Term Potentiation in Hippocampal Neurons, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/32237183\/."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.1093\/emboj\/cdf503","article-title":"Single-molecule investigation of the interference between kinesin, tau and MAP2c","volume":"21","author":"Seitz","year":"2002","journal-title":"EMBO J."},{"key":"ref_97","unstructured":"(2025, March 27). More than a Marker: Potential Pathogenic Functions of MAP2, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/36187353\/."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"16292","DOI":"10.1074\/jbc.M116.726547","article-title":"Crystal Structures of the Human Doublecortin C- and N-terminal Domains in Complex with Specific Antibodies","volume":"291","author":"Burger","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"34442","DOI":"10.1074\/jbc.M007078200","article-title":"Patient mutations in doublecortin define a repeated tubulin-binding domain","volume":"275","author":"Taylor","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1523\/JNEUROSCI.4603-12.2013","article-title":"Doublecortin (Dcx) family proteins regulate filamentous actin structure in developing neurons","volume":"33","author":"Fu","year":"2013","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1083\/jcb.201007081","article-title":"Template-free 13-protofilament microtubule-MAP assembly visualized at 8 A resolution","volume":"191","author":"Fourniol","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.molcel.2012.06.025","article-title":"Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins","volume":"47","author":"Liu","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.molcel.2004.06.009","article-title":"Mechanism of microtubule stabilization by doublecortin","volume":"14","author":"Moores","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.cub.2016.04.020","article-title":"Doublecortin Is Excluded from Growing Microtubule Ends and Recognizes the GDP-Microtubule Lattice","volume":"26","author":"Ettinger","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/jnc.14011","article-title":"Microtubule dynamics and the neurodegenerative triad of Alzheimer\u2019s disease: The hidden connection","volume":"143","author":"Brandt","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0022-2836(63)80008-X","article-title":"Electron microscope studies on the structure of natural and synthetic protein filaments from striated muscle","volume":"7","author":"Huxley","year":"1963","journal-title":"J. Mol. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0012-1606(76)90281-5","article-title":"Actin accumulation in developing chick brain and other tissues","volume":"54","author":"Santerre","year":"1976","journal-title":"Dev. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0014-4827(83)90213-6","article-title":"Actin polymerization and synthesis in cultured neurones","volume":"147","author":"Clark","year":"1983","journal-title":"Exp. Cell Res."},{"key":"ref_109","first-page":"65","article-title":"Actin in axons: Stable scaffolds and dynamic filaments","volume":"48","author":"Letourneau","year":"2009","journal-title":"Results Probl. Cell Differ."},{"key":"ref_110","unstructured":"(2025, March 27). Control of Synapse Structure and Function by Actin and Its Regulators, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/35203254\/."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0065-227X(90)90007-G","article-title":"Actin polymerization and ATP hydrolysis","volume":"26","author":"Carlier","year":"1990","journal-title":"Adv. Biophys."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.1175862","article-title":"Actin, a central player in cell shape and movement","volume":"326","author":"Pollard","year":"2009","journal-title":"Science"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nrm2679","article-title":"The trip of the tip: Understanding the growth cone machinery","volume":"10","author":"Lowery","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1021\/bi026520j","article-title":"Mechanism of formin-induced nucleation of actin filaments","volume":"42","author":"Pring","year":"2003","journal-title":"Biochemistry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/cm.20379","article-title":"Review of the mechanism of processive actin filament elongation by formins","volume":"66","author":"Paul","year":"2009","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.bpj.2012.03.003","article-title":"Membrane tension, myosin force, and actin turnover maintain actin treadmill in the nerve growth cone","volume":"102","author":"Craig","year":"2012","journal-title":"Biophys. J."},{"key":"ref_117","unstructured":"(2025, March 27). Mechanochemical Regulation of Growth Cone Motility, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/26217175\/."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mcn.2017.03.001","article-title":"Actin-based growth cone motility and guidance","volume":"84","author":"Omotade","year":"2017","journal-title":"Mol. Cell Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.brainresbull.2022.10.019","article-title":"Regulation of actin filament assembly and disassembly in growth cone motility and axon guidance","volume":"192","author":"Schneider","year":"2023","journal-title":"Brain Res. Bull."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0896-6273(95)90220-1","article-title":"Growth cone advance is inversely proportional to retrograde F-actin flow","volume":"14","author":"Lin","year":"1995","journal-title":"Neuron"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Craig, E.M., Stricker, J., Gardel, M., and Mogilner, A. (2015). Model for adhesion clutch explains biphasic relationship between actin flow and traction at the cell leading edge. Phys. Biol., 12.","DOI":"10.1088\/1478-3975\/12\/3\/035002"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1523\/JNEUROSCI.2645-15.2016","article-title":"Guidance of Axons by Local Coupling of Retrograde Flow to Point Contact Adhesions","volume":"36","author":"Nichol","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"ENEURO.0536-20.2021","DOI":"10.1523\/ENEURO.0536-20.2021","article-title":"Neuron Replating, a Powerful and Versatile Approach to Study Early Aspects of Neuron Differentiation","volume":"8","author":"Schneider","year":"2021","journal-title":"eNeuro"},{"key":"ref_124","unstructured":"(2025, March 27). Attention-Deficit\/Hyperactivity Disorder-Like Phenotype in a Mouse Model with Impaired Actin Dynamics, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/24768258\/."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/ncb1367","article-title":"Myosin II functions in actin-bundle turnover in neuronal growth cones","volume":"8","author":"Medeiros","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_126","unstructured":"(2025, March 27). Myosin 1b Promotes Axon Formation by Regulating Actin Wave Propagation and Growth Cone Dynamics, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/29588377\/."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2174\/156720510791050902","article-title":"ADF\/Cofilin-actin rods in neurodegenerative diseases","volume":"7","author":"Bamburg","year":"2010","journal-title":"Curr. Alzheimer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"113481","DOI":"10.1016\/j.bbr.2021.113481","article-title":"Role of RhoA\/ROCK signaling in Alzheimer\u2019s disease","volume":"414","author":"Cai","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1523\/JNEUROSCI.12-07-02685.1992","article-title":"Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation","volume":"12","author":"Harris","year":"1992","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Izeddin, I., Specht, C.G., Lelek, M., Darzacq, X., Triller, A., Zimmer, C., and Dahan, M. (2011). Super-resolution dynamic imaging of dendritic spines using a low-affinity photoconvertible actin probe. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0015611"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1523\/JNEUROSCI.09-08-02982.1989","article-title":"Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: Serial electron microscopy with reference to their biophysical characteristics","volume":"9","author":"Harris","year":"1989","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_132","unstructured":"(2025, March 27). Dendritic Spine Geometry is Critical for AMPA Receptor Expression in Hippocampal CA1 Pyramidal Neurons, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/11687814\/."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/10172","article-title":"Different modes of expression of AMPA and NMDA receptors in hippocampal synapses","volume":"2","author":"Takumi","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.neuron.2005.03.015","article-title":"Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites","volume":"46","author":"Noguchi","year":"2005","journal-title":"Neuron"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Lamprecht, R. (2021). Actin Cytoskeleton Role in the Maintenance of Neuronal Morphology and Long-Term Memory. Cells, 10.","DOI":"10.3390\/cells10071795"},{"key":"ref_136","first-page":"420","article-title":"Axo-somatic and axo-dendritic synapses of the cerebral cortex: An electron microscope study","volume":"93","author":"Gray","year":"1959","journal-title":"J. Anat."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nature02617","article-title":"Structural basis of long-term potentiation in single dendritic spines","volume":"429","author":"Matsuzaki","year":"2004","journal-title":"Nature"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.neuron.2004.11.011","article-title":"Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses","volume":"44","author":"Zhou","year":"2004","journal-title":"Neuron"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1083\/jcb.201003008","article-title":"Actin in dendritic spines: Connecting dynamics to function","volume":"189","author":"Hotulainen","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1083\/jcb.97.4.1169","article-title":"Cytoplasmic organization in cerebellar dendritic spines","volume":"97","author":"Landis","year":"1983","journal-title":"J. Cell Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1083\/jcb.95.1.345","article-title":"Cytoplasmic actin in neuronal processes as a possible mediator of synaptic plasticity","volume":"95","author":"Delay","year":"1982","journal-title":"J. Cell Biol."},{"key":"ref_142","unstructured":"(2025, March 27). Actin, Spectrin, and Associated Proteins Form a Periodic Cytoskeletal Structure in Axons, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/23239625\/."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.celrep.2015.02.007","article-title":"STED nanoscopy reveals the ubiquity of subcortical cytoskeleton periodicity in living neurons","volume":"10","author":"Kamin","year":"2015","journal-title":"Cell Rep."},{"key":"ref_144","unstructured":"(2025, March 27). Periodic F-Actin Structures Shape the Neck of Dendritic Spines, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/27841352\/."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/35010008","article-title":"Direct observation of dendritic actin filament networks nucleated by Arp2\/3 complex and WASP\/Scar proteins","volume":"404","author":"Blanchoin","year":"2000","journal-title":"Nature"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.1523\/JNEUROSCI.0035-13.2013","article-title":"Disruption of Arp2\/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities","volume":"33","author":"Kim","year":"2013","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_147","unstructured":"(2025, March 27). Defining Mechanisms of Actin Polymerization and Depolymerization During Dendritic Spine Morphogenesis, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/19380880\/."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"12753","DOI":"10.1074\/jbc.274.18.12753","article-title":"Ca2+\/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation","volume":"274","author":"Fleming","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_149","unstructured":"(2025, March 27). RICS, a Novel GTPase-Activating Protein for Cdc42 and Rac1, is Involved in the Beta-Catenin-N-Cadherin and N-Methyl-D-Aspartate Receptor Signaling, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/12531901\/."},{"key":"ref_150","unstructured":"(2025, March 27). The Rac1-GEF Tiam1 Couples the NMDA Receptor to the Activity-Dependent Development of Dendritic Arbors and Spines, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/15721239\/."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.neuron.2007.10.005","article-title":"Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines","volume":"56","author":"Xie","year":"2007","journal-title":"Neuron"},{"key":"ref_152","unstructured":"(2025, March 27). Local, Persistent Activation of Rho GTPases During Plasticity of Single Dendritic Spines, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/21423166\/."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/emboj.2008.34","article-title":"Arp2\/3 complex interactions and actin network turnover in lamellipodia","volume":"27","author":"Lai","year":"2008","journal-title":"EMBO J."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1126\/science.1094561","article-title":"Cofilin promotes actin polymerization and defines the direction of cell motility","volume":"304","author":"Ghosh","year":"2004","journal-title":"Science"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1146\/annurev.biochem.76.060805.160029","article-title":"The postsynaptic architecture of excitatory synapses: A more quantitative view","volume":"76","author":"Sheng","year":"2007","journal-title":"Annu. Rev. Biochem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nature12630","article-title":"SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties","volume":"503","author":"Han","year":"2013","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.15252\/embj.201488837","article-title":"Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion","volume":"33","author":"Chazeau","year":"2014","journal-title":"EMBO J."},{"key":"ref_158","unstructured":"(2025, May 23). Role of Cofilin in Alzheimer\u2019s Disease, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/33324642\/."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.3233\/JAD-190585","article-title":"Cofilin, a Master Node Regulating Cytoskeletal Pathogenesis in Alzheimer\u2019s Disease","volume":"72","author":"Kang","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"15772","DOI":"10.1523\/JNEUROSCI.1735-15.2015","article-title":"KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation","volume":"35","author":"Chevy","year":"2015","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.conb.2010.06.009","article-title":"A network of networks: Cytoskeletal control of compartmentalized function within dendritic spines","volume":"20","author":"Frost","year":"2010","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1038\/s41467-017-02230-8","article-title":"Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau","volume":"8","author":"Kadavath","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Quintanilla, R.A., Tapia-Monsalves, C., Vergara, E.H., P\u00e9rez, M.J., and Aranguiz, A. (2020). Truncated Tau Induces Mitochondrial Transport Failure Through the Impairment of TRAK2 Protein and Bioenergetics Decline in Neuronal Cells. Front. Cell Neurosci., 14.","DOI":"10.3389\/fncel.2020.00175"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1093\/brain\/awaa098","article-title":"Neurofilaments: Neurobiological foundations for biomarker applications","volume":"143","author":"Gafson","year":"2020","journal-title":"Brain J. Neurol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ceb.2020.10.011","article-title":"The dazzling rise of neurofilaments: Physiological functions and roles as biomarkers","volume":"68","author":"Bomont","year":"2021","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Yuan, A., and Nixon, R.A. (2021). Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.689938"},{"key":"ref_167","unstructured":"(2025, March 27). Neurofilament Light Chain as a Biomarker for Diagnosis of Multiple Sclerosis, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/34602928\/."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Verde, F., Otto, M., and Silani, V. (2021). Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.679199"},{"key":"ref_169","unstructured":"(2025, March 27). Neurofilaments as Biomarkers in Neurological Disorders\u2014Towards Clinical Application, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/38609644\/."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1152\/jn.00398.2021","article-title":"Phosphorylated neurofilament heavy chain: A potential diagnostic biomarker in amyotrophic lateral sclerosis","volume":"127","author":"Heckler","year":"2022","journal-title":"J. Neurophysiol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1242\/jcs.113.21.3861","article-title":"The C-terminal tail domain of neurofilament protein-H (NF-H) forms the crossbridges and regulates neurofilament bundle formation","volume":"113","author":"Chen","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1083\/jcb.200202037","article-title":"Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport","volume":"158","author":"Rao","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1083\/jcb.200308076","article-title":"The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate","volume":"163","author":"Rao","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1083\/jcb.108.4.1495","article-title":"Assembly and exchange of intermediate filament proteins of neurons: Neurofilaments are dynamic structures","volume":"108","author":"Angelides","year":"1989","journal-title":"J. Cell Biol."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"van Asperen, J.V., Kotaich, F., Caillol, D., and Bomont, P. (2024). Neurofilaments: Novel findings and future challenges. Curr. Opin. Cell Biol., 87.","DOI":"10.1016\/j.ceb.2024.102326"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"102566","DOI":"10.1016\/j.arr.2024.102566","article-title":"Molecular mechanisms of neurofilament alterations and its application in assessing neurodegenerative disorders","volume":"102","author":"Devarakonda","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"11316","DOI":"10.1523\/JNEUROSCI.1942-09.2009","article-title":"Neurofilaments form a highly stable stationary cytoskeleton after reaching a critical level in axons","volume":"29","author":"Yuan","year":"2009","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_178","unstructured":"(2025, March 27). Local Control of Neurofilament Accumulation During Radial Growth of Myelinating Axons In Vivo. Selective Role of Site-Specific Phosphorylation, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/11086003\/."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1083\/jcb.121.2.387","article-title":"Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene","volume":"121","author":"Ohara","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/BF00293376","article-title":"Hereditary hypotrophic axonopathy with neurofilament deficiency in a mutant strain of the Japanese quail","volume":"82","author":"Yamasaki","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"382107","DOI":"10.1155\/2012\/382107","article-title":"Neurofilament Phosphorylation during Development and Disease: Which Came First, the Phosphorylation or the Accumulation?","volume":"2012","author":"Dale","year":"2012","journal-title":"J. Amino Acids"},{"key":"ref_182","unstructured":"(2025, March 27). Reduced Diameter and Conduction Velocity of Myelinated Fibers in the Sciatic Nerve of a Neurofilament-Deficient Mutant Quail, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/8510825\/."},{"key":"ref_183","unstructured":"(2025, March 27). Electrophysiological Properties of Axons in Mice Lacking Neurofilament Subunit Genes: Disparity Between Conduction Velocity and Axon Diameter in Absence of NF-H, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/11121527\/."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1006\/exnr.2000.7378","article-title":"Altered ionic conductances in axons of transgenic mouse expressing the human neurofilament heavy gene: A mouse model of amyotrophic lateral sclerosis","volume":"163","author":"Kriz","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1073\/pnas.82.12.4274","article-title":"Aberrant neurofilament phosphorylation in Alzheimer disease","volume":"82","author":"Sternberger","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0006-8993(91)91528-9","article-title":"Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. III. Alterations following single and continuous beta, beta\u2019-iminodipropionitrile administrations","volume":"563","author":"Gold","year":"1991","journal-title":"Brain Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bbrc.2009.04.045","article-title":"Microtubule-independent regulation of neurofilament interactions in vitro by neurofilament-bound ATPase activities","volume":"384","author":"Leterrier","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1083\/jcb.143.1.183","article-title":"Disruption of the NF-H gene increases axonal microtubule content and velocity of neurofilament transport: Relief of axonopathy resulting from the toxin beta, beta\u2019-iminodipropionitrile","volume":"143","author":"Zhu","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1091\/mbc.11.10.3495","article-title":"Bidirectional translocation of neurofilaments along microtubules mediated in part by dynein\/dynactin","volume":"11","author":"Shah","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nbt0303-255","article-title":"Proteomic analysis of post-translational modifications","volume":"21","author":"Mann","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_191","first-page":"35","article-title":"Post-translational modifications and their biological functions: Proteomic analysis and systematic approaches","volume":"37","author":"Seo","year":"2004","journal-title":"J. Biochem. Mol. Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"7342","DOI":"10.1002\/anie.200501023","article-title":"Protein posttranslational modifications: The chemistry of proteome diversifications","volume":"44","author":"Walsh","year":"2005","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.cell.2020.10.029","article-title":"Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer\u2019s Disease","volume":"183","author":"Wesseling","year":"2020","journal-title":"Cell"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"6611","DOI":"10.1021\/jacs.8b02668","article-title":"Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States","volume":"140","author":"Lashuel","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/embj.201385876","article-title":"Co-regulation proteomics reveals substrates and mechanisms of APC\/C-dependent degradation","volume":"33","author":"Singh","year":"2014","journal-title":"EMBO J."},{"key":"ref_196","unstructured":"(2025, March 27). Acetylation of Tau Inhibits its Degradation and Contributes to Tauopathy, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/20869593\/."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/ncomms1255","article-title":"The acetylation of tau inhibits its function and promotes pathological tau aggregation","volume":"2","author":"Cohen","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2016.03.005","article-title":"Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss","volume":"90","author":"Tracy","year":"2016","journal-title":"Neuron"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"24978","DOI":"10.1074\/jbc.M501565200","article-title":"Sites of tau important for aggregation populate \u03b2-structure and bind to microtubules and polyanions","volume":"280","author":"Mukrasch","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41591-021-01251-7","article-title":"Author Correction: Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease","volume":"27","author":"Dujardin","year":"2021","journal-title":"Nat. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.molcel.2006.06.026","article-title":"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey","volume":"23","author":"Kim","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_202","unstructured":"(2025, March 27). The Growing Landscape of Lysine Acetylation Links Metabolism and Cell Signalling, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/25053359\/."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/nsmb.2555","article-title":"The microtubule-associated tau protein has intrinsic acetyltransferase activity","volume":"20","author":"Cohen","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1083\/jcb.124.5.769","article-title":"Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau","volume":"124","author":"Goode","year":"1994","journal-title":"J. Cell Biol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/nn.4067","article-title":"Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice","volume":"18","author":"Morris","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_206","unstructured":"(2025, March 27). Cryo-EM Structures of Tau Filaments from Alzheimer\u2019s Disease, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/28678775\/."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2020.01.027","article-title":"Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains","volume":"180","author":"Arakhamia","year":"2020","journal-title":"Cell"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"15692","DOI":"10.1021\/bi061422+","article-title":"Characterization of two VQIXXK motifs for tau fibrillization in vitro","volume":"45","author":"Li","year":"2006","journal-title":"Biochemistry"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nchem.2889","article-title":"Structure-based inhibitors of tau aggregation","volume":"10","author":"Seidler","year":"2018","journal-title":"Nat. Chem."},{"key":"ref_210","unstructured":"(2025, March 27). Acetylation Mimic of Lysine 280 Exacerbates Human Tau Neurotoxicity In Vivo, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/26940749\/."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13024-016-0109-0","article-title":"Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment","volume":"11","author":"Sohn","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"109037","DOI":"10.1016\/j.celrep.2021.109037","article-title":"Tau seeds are subject to aberrant modifications resulting in distinct signatures","volume":"35","author":"Tseng","year":"2021","journal-title":"Cell Rep."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1021\/jz501457f","article-title":"Structural Insight into Tau Protein\u2019s Paradox of Intrinsically Disordered Behavior, Self-Acetylation Activity, and Aggregation","volume":"5","author":"Luo","year":"2014","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40478-018-0651-9","article-title":"A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response","volume":"7","author":"Guo","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Tracy, T.E., and Gan, L. (2017). Acetylated tau in Alzheimer\u2019s disease: An instigator of synaptic dysfunction underlying memory loss: Increased levels of acetylated tau blocks the postsynaptic signaling required for plasticity and promotes memory deficits associated with tauopathy. BioEssays News Rev. Mol. Cell Dev. Biol., 39.","DOI":"10.1002\/bies.201600224"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1039\/D1CS00991E","article-title":"Dissecting the role of protein phosphorylation: A chemical biology toolbox","volume":"51","author":"Bilbrough","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.arr.2012.06.003","article-title":"Tau protein kinases: Involvement in Alzheimer\u2019s disease","volume":"12","author":"Martin","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_218","unstructured":"(2025, March 27). Tau Protein Phosphatases in Alzheimer\u2019s Disease: The Leading Role of PP2A, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/22771380\/."},{"key":"ref_219","unstructured":"(2025, March 27). Mechanisms of Tau-Induced Neurodegeneration, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/19184068\/."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbadis.2004.06.017","article-title":"Tau phosphorylation: Physiological and pathological consequences","volume":"1739","author":"Stoothoff","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1021\/acscentsci.1c00585","article-title":"A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms","volume":"7","author":"Brotzakis","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"ref_222","unstructured":"(2025, March 27). An Acetylation-Phosphorylation Switch that Regulates Tau Aggregation Propensity and Function, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/28760828\/."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s004010100423","article-title":"Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer\u2019s disease","volume":"103","author":"Augustinack","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neuron.2013.02.003","article-title":"The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of A\u03b2 oligomers through Tau phosphorylation","volume":"78","author":"Courchet","year":"2013","journal-title":"Neuron"},{"key":"ref_225","first-page":"7679","article-title":"Microtubule-associated protein\/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262","volume":"270","author":"Drewes","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neuroscience.2016.03.044","article-title":"Tau pathology-mediated presynaptic dysfunction","volume":"325","author":"Moreno","year":"2016","journal-title":"Neuroscience"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Durairajan, S.S.K., Selvarasu, K., Singh, A.K., Patnaik, S., Iyaswamy, A., Jaiswal, Y., Williams, L.L., and Huang, J.D. (2024). Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer\u2019s disease. Front. Cell Neurosci., 18.","DOI":"10.3389\/fncel.2024.1432002"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrm2673","article-title":"Ubiquitin-like protein activation by E1 enzymes: The apex for downstream signalling pathways","volume":"10","author":"Schulman","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41584-022-00778-4","article-title":"Disorders of ubiquitylation: Unchained inflammation","volume":"18","author":"Beck","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"e1800108","DOI":"10.1002\/pmic.201800108","article-title":"Quantitative Analysis of the Brain Ubiquitylome in Alzheimer\u2019s Disease","volume":"18","author":"Abreha","year":"2018","journal-title":"Proteomics"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.bbadis.2014.05.029","article-title":"Axotrophin\/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding","volume":"1842","author":"Flach","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_232","unstructured":"(2025, March 27). Alzheimer Disease-Specific Conformation of Hyperphosphorylated Paired Helical Filament-Tau is Polyubiquitinated Through Lys-48, Lys-11, and Lys-6 Ubiquitin Conjugation, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/16443603\/."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"265","DOI":"10.5483\/BMBRep.2018.51.6.077","article-title":"Degradation or aggregation: The ramifications of post-translational modifications on tau","volume":"51","author":"Park","year":"2018","journal-title":"BMB Rep."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0006-8993(91)90681-K","article-title":"Abnormal phosphorylation of tau precedes ubiquitination in neurofibrillary pathology of Alzheimer disease","volume":"539","author":"Bancher","year":"1991","journal-title":"Brain Res."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/j.1750-3639.2011.00525.x","article-title":"Ubiquitin is associated with early truncation of tau protein at aspartic acid421 during the maturation of neurofibrillary tangles in Alzheimer\u2019s disease","volume":"22","author":"Kristofikova","year":"2012","journal-title":"Brain Pathol."},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Alquezar, C., Arya, S., and Kao, A.W. (2020). Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.595532"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Li, L., Jiang, Y., Wang, J.Z., Liu, R., and Wang, X. (2021). Tau Ubiquitination in Alzheimer\u2019s Disease. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.786353"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00401-011-0893-0","article-title":"Dual modification of Alzheimer\u2019s disease PHF-tau protein by lysine methylation and ubiquitylation: A mass spectrometry approach","volume":"123","author":"Thomas","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"16586","DOI":"10.1073\/pnas.1417548111","article-title":"SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination","volume":"111","author":"Luo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Matsuzaki, S., Lee, L., Knock, E., Srikumar, T., Sakurai, M., Hazrati, L.N., Katayama, T., Staniszewski, A., Raught, B., and Arancio, O. (2015). SUMO1 Affects Synaptic Function, Spine Density and Memory. Sci. Rep., 5.","DOI":"10.1038\/srep10730"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"9919","DOI":"10.1074\/jbc.M510127200","article-title":"Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and alpha-synuclein","volume":"281","author":"Dorval","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"e14481","DOI":"10.1002\/alz.14481","article-title":"Lactylation of tau in human Alzheimer\u2019s disease brains","volume":"21","author":"Zhang","year":"2025","journal-title":"Alzheimers Dement. J. Alzheimers Assoc."},{"key":"ref_243","unstructured":"(2025, May 23). Distinct Regulation of Tau Monomer and Aggregate Uptake and Intracellular Accumulation in Human Neurons, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/39736627\/."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"e14418","DOI":"10.1002\/alz.14418","article-title":"Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms","volume":"21","author":"Falkon","year":"2025","journal-title":"Alzheimers Dement. J. Alzheimers Assoc."},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Woo, J.A.A., Liu, T., Fang, C.C., Cazzaro, S., Kee, T., LePochat, P., Yrigoin, K., Penn, C., Zhao, X., and Wang, X. (2019). Activated cofilin exacerbates tau pathology by impairing tau-mediated microtubule dynamics. Commun. Biol., 2.","DOI":"10.1038\/s42003-019-0359-9"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.1016\/0197-4580(94)90179-1","article-title":"Microtubule stabilizing drugs for the treatment of Alzheimer\u2019s disease","volume":"15","author":"Lee","year":"1994","journal-title":"Neurobiol. Aging"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"13861","DOI":"10.1523\/JNEUROSCI.3059-10.2010","article-title":"Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy","volume":"30","author":"Brunden","year":"2010","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1523\/JNEUROSCI.4922-11.2012","article-title":"The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice","volume":"32","author":"Zhang","year":"2012","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2174\/156720509789207895","article-title":"Addressing Alzheimer\u2019s disease tangles: From NAP to AL-108","volume":"6","author":"Gozes","year":"2009","journal-title":"Curr. Alzheimer Res."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1159\/000348347","article-title":"A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment","volume":"35","author":"Morimoto","year":"2013","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1002\/alz.13875","article-title":"A small-molecule microtubule-stabilizing agent safely reduces A\u03b2 plaque and tau pathology in transgenic mouse models of Alzheimer\u2019s disease","volume":"20","author":"Yao","year":"2024","journal-title":"Alzheimers Dement. J. Alzheimers Assoc."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"10349","DOI":"10.1523\/JNEUROSCI.1409-18.2018","article-title":"Synaptotoxicity in Alzheimer\u2019s Disease Involved a Dysregulation of Actin Cytoskeleton Dynamics through Cofilin 1 Phosphorylation","volume":"38","author":"Rush","year":"2018","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.1523\/JNEUROSCI.5567-05.2006","article-title":"Phosphorylation of actin-depolymerizing factor\/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: A potential mechanism of neuronal dystrophy in Alzheimer\u2019s disease","volume":"26","author":"Heredia","year":"2006","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"115573","DOI":"10.1016\/j.addr.2025.115573","article-title":"Intranasal NAP (Davunetide): Neuroprotection and circadian rhythmicity","volume":"220","author":"Galushkin","year":"2025","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"115524","DOI":"10.1016\/j.bbr.2025.115524","article-title":"Role of RhoA-ROCK signaling inhibitor fasudil in Alzheimer disease","volume":"484","author":"Sulaiman","year":"2025","journal-title":"Behav. Brain Res."},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Singh, Y.P., and Kumar, H. (2024). Recent Advances in Medicinal Chemistry of Memantine Against Alzheimer\u2019s Disease. Chem. Biol. Drug Des., 104.","DOI":"10.1111\/cbdd.14638"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1001\/jamaneurol.2019.3812","article-title":"Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients with Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome: A Randomized Clinical Trial","volume":"77","author":"Tsai","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"e13081","DOI":"10.1111\/acel.13081","article-title":"Acetylation changes tau interactome to degrade tau in Alzheimer\u2019s disease animal and organoid models","volume":"19","author":"Choi","year":"2020","journal-title":"Aging Cell"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1212\/WNL.0000000000207861","article-title":"Semorinemab in Mild-to-Moderate Alzheimer Disease: A Glimmer of Hope Though Cautions Remain","volume":"101","author":"Edland","year":"2023","journal-title":"Neurology"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1001\/jamaneurol.2022.1375","article-title":"Safety and Efficacy of Semorinemab in Individuals With Prodromal to Mild Alzheimer Disease: A Randomized Clinical Trial","volume":"79","author":"Teng","year":"2022","journal-title":"JAMA Neurol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/831\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:47:59Z","timestamp":1760032079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":260,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biom15060831"],"URL":"https:\/\/doi.org\/10.3390\/biom15060831","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}