mProX™ Human TTBK2 Stable Cell Line

Yukawa, Kayo. et al. "Antisense oligonucleotide-based targeting of Tau-tubulin kinase 1 prevents hippocampal accumulation of phosphorylated tau in PS19 tauopathy mice." Acta neuropathologica communications, 2023.
Tau tubulin kinase-1 (TTBK1) is a neuron-specific tau kinase that is highly expressed in the entorhinal cortex and hippocampal regions, where early tau pathology occurs in Alzheimer's disease (AD). Recent research has shown that the protein expression level of TTBK1 is elevated in the cortex brain tissues of AD patients compared to control subjects. Researchers hypothesized that targeting Ttbk1 using antisense oligonucleotides (ASO) could prevent the accumulation of phosphorylated tau and potentially delay the development of tau pathology in AD. In vivo experiments using PS19 tau transgenic mice showed that central administration of ASO-Ttbk1 specifically suppressed the expression of Ttbk1 without affecting Ttbk2 expression in the temporal cortex. Furthermore, ASO-Ttbk1 treatment significantly reduced the expression level of phospho-tau epitopes relevant to AD and decreased the intensity of pS422 phosphorylated tau in the dentate gyrus region of the hippocampus. RNA-sequence analysis revealed that ASO-Ttbk1 treatment resulted in enrichment of interferon-gamma and complement pathways and increased expression of antigen presenting molecules in the temporal cortex tissue, suggesting a potential effect on microglial phenotype without neurotoxicity. These findings suggest that TTBK1 is a promising therapeutic target for suppressing TTBK1 expression and pathological tau phosphorylation in the early stages of AD.
Yukawa, Kayo. et al. "Antisense oligonucleotide-based targeting of Tau-tubulin kinase 1 prevents hippocampal accumulation of phosphorylated tau in PS19 tauopathy mice." Acta neuropathologica communications, 2023.
Pubmed: 37853497   DOI: 10.1186/s40478-023-01661-3

Lu, Yin-Qian. et al. "A Novel TTBK2 Mutation in a Chinese Pedigree with Spinocerebellar Ataxia 11." Cerebellum (London, England), 2023.
Spinocerebellar ataxia type 11 (SCA11) is a rare disorder caused by mutations in the tau tubulin kinase 2 (TTBK2) gene. Despite this, there have only been six reported cases of SCA11 in families. A new Chinese SCA11 pedigree with two individuals showing symptoms of cerebellar ataxia was studied. Clinical and imaging tests revealed typical features of cerebellar ataxia and atrophy. Using whole-exome sequencing (WES), researchers identified a novel heterozygous duplication mutation (c.1211_1217dupAGGAGAA) in the TTBK2 gene in the proband. This frame-shift mutation resulted in a premature stop codon (p. N406Kfs*47). The proband's affected brother was also found to have the mutation, while their unaffected mother carried the mutation with a lower percentage and displayed no symptoms. This study expands the known genotypic spectrum of SCA11.
Lu, Yin-Qian. et al. "A Novel TTBK2 Mutation in a Chinese Pedigree with Spinocerebellar Ataxia 11." Cerebellum (London, England), 2023.
Pubmed: 37848700   DOI: 10.1007/s12311-023-01616-3