Ttbk1, short for Tau-tubulin kinase 1, belongs to the casein kinase superfamily. It is specifically expressed in the central nervous system. Ttbk1 phosphorylates microtubule-associated protein tau, especially at Ser422, and also activates cycline-dependent kinase 5 in a unique way. It is involved in the phosphorylation and aggregation of tau, and is linked to the pathobiology of tauopathy including Alzheimer's disease (AD) [1].

In AD research, Ttbk1 transgenic mice harboring the entire 55-kilobase genomic sequence of human Ttbk1, when crossed with tau mutant mice, show progression of tau accumulation, neuroinflammation, and neurodegeneration. This indicates Ttbk1's role in mediating M1-activated microglia-induced neurotoxicity and its overexpression can lead to axonal degeneration in vitro [1].

In conclusion, Ttbk1 is an important molecule in the central nervous system, with its functions centered around tau phosphorylation and aggregation. Studies using transgenic mouse models have revealed its significance in the development of neurodegenerative diseases, especially AD, providing insights into the underlying mechanisms and potential therapeutic targets for these diseases.

References:

1. Ikezu, Seiko, Ikezu, Tsuneya. 2014. Tau-tubulin kinase. In Frontiers in molecular neuroscience, 7, 33. doi:10.3389/fnmol.2014.00033. https://pubmed.ncbi.nlm.nih.gov/24808823/