Proteins are macromolecules that play an important role in almost any cellular process. They usually do not work alone, but rather as complexes with other molecules, mainly other proteins. Tau proteins belong to the family of microtubule-associated proteins (MAPs) and may be related to axonal transport and growth, neuronal polarization and, therefore, the normal functioning of neurons and the brain.
Tau protein can be found mainly in neurons, but also, although in smaller amounts, in oligodendrocytes and astrocytes. It is present mainly in the central nervous system (CNS), although it is also expressed in the peripheral nervous system. Tau can be expressed in 6 different isoforms, with lengths varying from 352 to 441 amino acids. The different conformations can be expressed at different stages of development and even vary according to the types or the state of maturation of the neurons.
The microtubule-stabilizing function of tau protein has been shown to be replaceable by the microtubule-associated proteins MAP1a or MAP1b. However, the absence of tau may influence the regulation of neuronal activity, synaptic plasticity, neurogenesis, iron export from neurons, and long-term depression of synapses.
One of the post-translational modifications is phosphorylation, the degree of which in all six isoforms decreases with age due to activation of phosphatases. Like the kinases, the phosphatases also play a role in the regulation of tau phosphorylation.
Hyperphosphorylation of tau protein (tau inclusions, pTau) can lead to self-assembly of filament tangles, which are implicated in the pathogenesis of Alzheimer’s disease, frontotemporal dementia, and other tauopathies. All six tau isoforms are present in an often hyperphosphorylated state in helical filaments in the brain with Alzheimer’s disease. When misfolded, this normally highly soluble protein can form extremely insoluble aggregates that contribute to some neurodegenerative diseases. Tau protein has a direct effect on the breakdown of living cells caused by accumulations that block nerve synapses.
Expression of the gender-specific tau gene in different regions of the human brain has recently been implicated in gender differences in the manifestations and risk of tauopathies. Some aspects of how the disease works also suggest that it has some similarities to prion proteins.
In this interesting Science Advances article, master points of mutations are described and how with the help of CRISPR they can be identified and truncated. Alzheimer’s disease: Ablating single master site abolishes tau hyperphosphorylation
Signalchem manufactures one of the most comprehensive selections of recombinant Tau proteins in the world. These include various isoforms of the proteins, phosphorylated taus, and mutant variants. This selection of a wide range of Tau proteins provides tools to facilitate research in neurobiology. These proteins have been used in a variety of fields including neurodegeneration, oncology, epigenetics, cellular stress, and more.
If you want more information about tau proteins or how Signalchem can help your research, do not hesitate to contact us:
Sinsky J, Pichlerova K, Hanes J. Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies. Int J Mol Sci. 2021 Aug 26;22(17):9207. doi: 10.3390/ijms22179207. PMID: 34502116; PMCID: PMC8431036.
Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K (June 2001). Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proceedings of the National Academy of Sciences of the United States of America. 98 (12): 6923–8. Bibcode:2001PNAS. 98.6923A. doi:10.1073/pnas.121119298
Mawal-Dewan M, Henley J, Van de Voorde A, Trojanowski JQ, Lee VM (December 1994). “The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases”. The Journal of Biological Chemistry. 269 (49): 30981–7. doi:10.1016/S0021-9258(18)47378-4