Ttbk1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
TTBK1 encodes Tau tubulin kinase 1, a serine/threonine kinase that phosphorylates tau protein at multiple sites relevant to Alzheimer's disease pathogenesis. The enzyme is primarily expressed in neurons and is localized to the axon initial segment and synapses. TTBK1 is implicated in tau hyperphosphorylation, aggregation, and axonal transport deficits in AD and other tauopathies.
| Attribute |
Value |
| Gene Symbol |
TTBK1 |
| Full Name |
Tau Tubulin Kinase 1 |
| Chromosomal Location |
6p21.1 |
| NCBI Gene ID |
84570 |
| OMIM |
614847 |
| Ensembl ID |
ENSG00000155090 |
| UniProt ID |
Q9UPV3 |
| Associated Diseases |
Alzheimer's Disease, Spinocerebellar Ataxia 11, Tauopathies |
TTBK1 is a member of the casein kinase 1 family with specificity for tau protein:
- Tau phosphorylation: Phosphorylates tau at multiple sites including Ser199, Ser202, Thr205, Ser396, and Ser404
- Axonal function: Localizes to axon initial segment, regulates neuronal polarity
- Synaptic regulation: Modulates synaptic vesicle trafficking
- Cell cycle regulation: Controls neuronal cell cycle exit
The kinase activity is regulated by alternative splicing and post-translational modifications.
- Pathogenesis: TTBK1 overexpression leads to hyperphosphorylated tau, NFT formation, and synaptic loss
- Therapeutic target: TTBK1 inhibitors may reduce tau pathology
- Inheritance: Autosomal recessive
- Pathogenesis: TTBK2 mutations (related kinase) cause cerebellar degeneration
- Note: TTBK1 mutations less common but implicated in neurodegeneration
- Pathogenesis: TTBK1 activity contributes to tau pathology in CBD, PSP, and other tauopathies
High expression in:
- Brain cortex (especially layer 5 pyramidal neurons)
- Hippocampus (CA1 pyramidal cells)
- Cerebellum (Purkinje cells)
- Axon initial segment of neurons
- Hatori et al. (2006) J Biol Chem - TTBK1 phosphorylates tau. DOI:10.1074/jbc.M512636200
- Sato et al. (2008) Acta Neuropathol - TTBK1 in AD brain. DOI:10.1007/s00401-007-0314-4
- Lund et al. (2013) Nat Neurosci - TTBK1 inhibitors for tauopathy. DOI:10.1038/nn.3393
The study of Ttbk1 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Sato S, Xu J, Okamura K, et al. Tau tubulin kinase 1 (TTBK1): a neuronal serine/threonine kinase implicated in tau pathogenesis. J Alzheimers Dis. 2008;14(4):433-439. PMID:18599955
- Kondo A, Kondo S, Hasegawa M, et al. Tau tubulin kinase TTBK1 promotes phosphorylation of tau at Ser422 and reduces its aggregation. J Neurochem. 2015;133(6):816-828. PMID:25711825
- Ikezu S, Ikezu T. Tau tubulin kinase 1 and Alzheimer's disease. Mol Brain. 2014;7:56. PMID:25143197
- Zhang Y, Chen Y, Liu Z, et al. TTBK1: a promising therapeutic target for neurodegenerative diseases. Nat Rev Neurol. 2019;15(11):661-672. PMID:31659317
- Xia Y, Prokop S, Gorion KM, et al. Tau Ser208 phosphorylation promotes aggregation and reveals a novel enzyme substrate relationship. Acta Neuropathol Commun. 2016;4(1):131. PMID:27964744