The Tau protein is a microtubule-associated protein expressed primarily in axons of central nervous system neurons. Tau is also detected in oligodendrocytes, the somatodendritic compartment within neurons, and some non-neuronal tissues. In healthy neurons, Tau promotes the assembly and stabilization of microtubules along with other MAP proteins, especially MAP1B. It is believed that other proteins can compensate for loss of Tau protein function as Tau knockout mice are viable and show no signs of neurodegeneration. There are multiple isoforms of Tau created by alternative splicing of exons 2, 3, and 10. And Tau protein is heavily phosphorylated throughout the protein mostly occurring on Ser-Pro and Thr-Pro motifs. Several kinases and phosphatases regulate the phosphorylation state of Tau.
Hyperphosphorylation of Tau is an underlying cause of tauopathies, a group of neurodegenerative diseases that are characterized by accumulation of misfolded Tau protein into neurofibrillary tangles (NFT). Alzheimer’s disease and Parkinson’s disease are two tauopathies. Hyperphosphorylated Tau protein exhibits lower affinity for microtubules resulting in destabilization of the cytoskeleton and a reduction in axonal transport. When Tau protein gets hyperphosphorylated, it promotes misfolding and oligomerization into NFT ultimately causing neuronal impairment and cell death.
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