Tauopathies

By Aarav Ghate | 1 October 2024

Tauopathies are a kind of neurodegenerative Disease (NDD) and a subclass of proteinopathies. They are characterised by the misfolding of the tau protein, which leads to aggregates of abnormal tau which manifest as neurofibrillary tangles.

Tau are microtubule associated proteins that are responsible for stabilisation of these tubules, which is important for axonal growth. Neuronal microtubules form the cytoskeleton of neurons, and are important in neuronal migration and differentiation. Tau undergoes phosphorylation at specific sites in order to bind with the microtubules as well as for other functions. However, in some cases the tau may get hyperphosphorylated which leads to abnormal interactions with microtubules as well as other tau proteins. A positive tau-tau interaction leads to the formation of aggregates known as neurofibrillary tangles.

Neurofibrillary tangles (NFTs) are known largely as a biomarker for Alzheimer’s Disease, however they develop in other tauopathies as well. In Alzheimer’s, the tau protein gets hyperphosphorylated (and is called p-Tau), and subsequently forms neurofibrillary tangles and paired helical filaments. These hamper axonal functions and lead to the degeneration of neurons. Interestingly, factors released by the presence of beta-amyloid aggregates (another biomarker of Alzheimer’s) may trigger p-Tau hyperphosphorylation and misfolding. The presence of beta-amyloid greatly impacts the neuron to neuron transport of the misfolded p-Tau protein. Hence, NFTs and p-Tau proteins are considered key biomarkers for Alzheimer’s, the most common among the tauopathies.

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Treatment of tauopathies focuses on decreasing protein aggregation and neurofibrillary tangles. The use of aptamers to bind to sites on the p-Tau protein in order to prevent phosphorylation is also being studied.

References:

  1. Govindaraju, T, Alzheimer’s Disease, Royal Society of Chemistry, (2022).
  2. Wang, Y. Mandelkow, E. Tau in Physiology and Pathology, Nature Reviews, (2016)
  3. Johnson, G. Stoothoff, W., Tau Phosphorylation, Journal of Cell Science, (2004)

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