Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology
The aggregation of Tau protein into neurofibrillary tangles (NFTs), a hallmark of Alzheimer’s 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 microt...
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MDPI AG
2025-06-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/6/831 |
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| author | Gege Jiang Guanfeng Xie Xiaoyi Li Jing Xiong |
| author_facet | Gege Jiang Guanfeng Xie Xiaoyi Li Jing Xiong |
| author_sort | Gege Jiang |
| collection | DOAJ |
| description | The aggregation of Tau protein into neurofibrillary tangles (NFTs), a hallmark of Alzheimer’s 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—such as phosphorylation, acetylation and ubiquitination—trigger 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 |
| format | Article |
| id | doaj-art-7ab8d97d84c94df3a67d3c7cefc358ec |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-7ab8d97d84c94df3a67d3c7cefc358ec2025-08-20T03:26:25ZengMDPI AGBiomolecules2218-273X2025-06-0115683110.3390/biom15060831Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau PathologyGege Jiang0Guanfeng Xie1Xiaoyi Li2Jing Xiong3Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaThe aggregation of Tau protein into neurofibrillary tangles (NFTs), a hallmark of Alzheimer’s 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—such as phosphorylation, acetylation and ubiquitination—trigger 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 ADhttps://www.mdpi.com/2218-273X/15/6/831Alzheimer’s diseaseearly stageneuronal cytoskeletontaupost-translationally modified |
| spellingShingle | Gege Jiang Guanfeng Xie Xiaoyi Li Jing Xiong Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology Biomolecules Alzheimer’s disease early stage neuronal cytoskeleton tau post-translationally modified |
| title | Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology |
| title_full | Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology |
| title_fullStr | Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology |
| title_full_unstemmed | Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology |
| title_short | Cytoskeletal Proteins and Alzheimer’s Disease Pathogenesis: Focusing on the Interplay with Tau Pathology |
| title_sort | cytoskeletal proteins and alzheimer s disease pathogenesis focusing on the interplay with tau pathology |
| topic | Alzheimer’s disease early stage neuronal cytoskeleton tau post-translationally modified |
| url | https://www.mdpi.com/2218-273X/15/6/831 |
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