Tau – an inhibitor of deacetylase HDAC6 function
Abstract
Analysis of brain microtubule protein from patients with Alzheimer’s disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation‐deacetylation of tubulin. Our results indicate that tau binds to the tubulin‐deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild‐type mice compared with tubulin from mice lacking tau because of the tau‐mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.
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Genetic deletion studies indicate that endogenous tau participates in neuronal processes including cytoskeletal regulation, mitochondrial dynamics, synaptic plasticity, network activity, and DNA/RNA stability.
“Genetic deletion studies indicate that endogenous tau participates in a range of neuronal processes, including cytoskeletal regulation, mitochondrial dynamics, synaptic plasticity, network activity [10–22], and stability of DNA and RNA stability [23].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [12]
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Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease
Chimal-Juárez, E., Patel, H., Jury-Garfe, N., Dabin, L. C., Vidal, R., Kim, J., & Lasagna-Reeves, C. A. (2026) · bioRxiv · doi:10.64898/2026.05.12.724684
- Authors
- Perez, M., Santa‐Maria, I., De Barreda, E. G., Zhu, X., Cuadros, R., Cabrero, J. R., Sanchez‐Madrid, F., Dawson, H. N., Vitek, M. P., Perry, G., Smith, M. A., & Avila, J.
- Affiliations
- Case Western Reserve University (US)
- Centro de Biología Molecular Severo Ochoa (ES)
- Duke University (US)
- The University of Texas at San Antonio (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-05-21
- Volume
- 109
- Issue
- 6
- Pages
- 1756-1766
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2067215332
- Cited by
- 182
- References
- 8
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 11 · 2019: 5 · 2018: 14 · 2017: 8 · 2016: 13 · 2015: 18 · 2014: 20 · 2013: 10 · 2012: 19
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- tau protein, HDAC6, tubulin acetylation, tubulin deacetylation, alpha-tubulin, neurofibrillary tangles, Alzheimer's disease, autophagy, proteasome inhibition, tau knockout mice, microtubules
- MeSH terms
- Histone Deacetylase 6, Acetylation, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Boronic Acids, Brain, Cells, Cultured, Embryo, Mammalian, Enzyme Inhibitors, Female, Gene Expression Regulation, Histone Deacetylases, Humans, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Neurons, Postmortem Changes, Transfection, Tubulin, tau Proteins, Mice, Knockout, Immunoprecipitation, Mice
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