Biochemistry and cell biology of tau protein in neurofibrillary degeneration
- PMID: 22762014
- PMCID: PMC3385935
- DOI: 10.1101/cshperspect.a006247
Biochemistry and cell biology of tau protein in neurofibrillary degeneration
Abstract
Tau represents the subunit protein of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications (phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming β structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.
Figures





Similar articles
-
Mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles.J Neural Transm Suppl. 1998;53:169-80. doi: 10.1007/978-3-7091-6467-9_15. J Neural Transm Suppl. 1998. PMID: 9700655 Review.
-
Tau mediated neurodegeneration: an insight into Alzheimer's disease pathology.Neurochem Res. 2011 Aug;36(8):1329-35. doi: 10.1007/s11064-011-0475-5. Epub 2011 Apr 21. Neurochem Res. 2011. PMID: 21509508 Review.
-
Tau pathology in Alzheimer disease and other tauopathies.Biochim Biophys Acta. 2005 Jan 3;1739(2-3):198-210. doi: 10.1016/j.bbadis.2004.09.008. Biochim Biophys Acta. 2005. PMID: 15615638 Review.
-
Role of microtubule-associated protein tau phosphorylation in Alzheimer's disease.J Huazhong Univ Sci Technolog Med Sci. 2017 Jun;37(3):307-312. doi: 10.1007/s11596-017-1732-x. Epub 2017 Jun 6. J Huazhong Univ Sci Technolog Med Sci. 2017. PMID: 28585125 Review.
-
Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration.J Alzheimers Dis. 2013;33 Suppl 1:S123-39. doi: 10.3233/JAD-2012-129031. J Alzheimers Dis. 2013. PMID: 22710920 Review.
Cited by
-
C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death.J Neurosci. 2015 Jul 29;35(30):10851-65. doi: 10.1523/JNEUROSCI.0387-15.2015. J Neurosci. 2015. PMID: 26224867 Free PMC article.
-
Deleterious Alteration of Glia in the Brain of Alzheimer's Disease.Int J Mol Sci. 2020 Sep 12;21(18):6676. doi: 10.3390/ijms21186676. Int J Mol Sci. 2020. PMID: 32932623 Free PMC article. Review.
-
Liquid-liquid phase separation in diseases.MedComm (2020). 2024 Jul 13;5(7):e640. doi: 10.1002/mco2.640. eCollection 2024 Jul. MedComm (2020). 2024. PMID: 39006762 Free PMC article. Review.
-
Cellular and pathological functions of tau.Nat Rev Mol Cell Biol. 2024 Nov;25(11):845-864. doi: 10.1038/s41580-024-00753-9. Epub 2024 Jul 16. Nat Rev Mol Cell Biol. 2024. PMID: 39014245 Review.
-
Metabolic control of the proteotoxic stress response: implications in diabetes mellitus and neurodegenerative disorders.Cell Mol Life Sci. 2016 Nov;73(22):4231-4248. doi: 10.1007/s00018-016-2291-1. Epub 2016 Jun 11. Cell Mol Life Sci. 2016. PMID: 27289378 Free PMC article. Review.
References
-
- Aamodt EJ, Williams RC Jr 1984. Microtubule-associated proteins connect microtubules and neurofilaments in vitro. Biochemistry 23: 6023–6031 - PubMed
-
- Ackmann M, Wiech H, Mandelkow E 2000. Nonsaturable binding indicates clustering of tau on the microtubule surface in a paired helical filament-like conformation. J Biol Chem 275: 30335–30343 - PubMed
-
- Aguzzi A, Rajendran L 2009. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 64: 783–790 - PubMed
-
- Ahn JS, Radhakrishnan ML, Mapelli M, Choi S, Tidor B, Cuny GD, Musacchio A, Yeh LA, Kosik KS 2005. Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation. Chem Biol 12: 811–823 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical