Introduction to Tau Proteins
Tau proteins are essential components of nerve cells and play an important role in preserving the structural integrity of microtubules14. Microtubules are required for the intracellular transport and organization of cellular structures. Alternative splicing of MAPT, which is located on chromosome 17q21.3, is the primary mechanism by which these proteins are created14,15. Tau proteins interact with tubulin to stabilize microtubules and govern their assembly, dynamic activity, and spatial organization16. These processes are controlled by the spatial structure of the microtubules. They are especially active in the distal regions of axons, where they increase microtubule flexibility by controlling phosphorylation14. This helps the axons transmit signals more efficiently.
The development of tangled filaments is a characteristic feature of Alzheimer’s disease (AD), which is caused by the hyperphosphorylation of tau proteins14,15. These tau tangles are a hallmark of the etiology of Alzheimer’s disease and contribute to the increasing neurodegeneration that is characteristic of the condition. All six isoforms of tau protein are hyperphosphorylated in the brain tissue of patients diagnosed with Alzheimer’s disease (AD).
Tau proteins can be found in a number of different isoforms, with three isoforms comprising three binding domains and the other three comprising four binding domains17. These binding domains make it easier for tau to engage directly with microtubules, which in turn stimulates microtubule polymerization and helps maintain the dynamics under control. In addition, tau proteins have a positive charge, which causes them to be drawn to microtubules that have a negative charge.
Post-translational changes, including phosphorylation, acetylation, oxidation, ubiquitination, methylation, glycosylation, and polyamination, can affect tau protein function18. Polyamination is a posttranslational process. These alterations can result in enhanced aggregation of tau proteins and creation of tau tangles, both of which contribute to the pathogenesis of Alzheimer’s disease16,18.
Understanding the function of tau proteins and their involvement in Alzheimer’s disease (AD) is essential for the development of specific therapeutic techniques that can combat the aberrant aggregation of tau proteins and alleviate some of the debilitating symptoms of this neurodegenerative condition. The ongoing research that is being conducted in this area has promise for expanding our knowledge of Alzheimer’s disease (AD) and possibly developing novel medicines to tackle this difficult condition.