Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration.

ABSTRACT:

Background

Progressive neuron loss in the frontal and temporal lobes of the cerebral cortex typifies frontotemporal lobar degeneration (FTLD). FTLD sub types are classified on the basis of neuronal aggregated protein deposits, typically containing either aberrantly phosphorylated TDP-43 or tau. Our recent work demonstrated that tau tubulin kinases 1 and 2 (TTBK1/2) robustly phosphorylate TDP-43 and co-localize with phosphorylated TDP-43 in human postmortem neurons from FTLD patients. Both TTBK1 and TTBK2 were initially identified as tau kinases and TTBK1 has been shown to phosphorylate tau epitopes commonly observed in Alzheimer's disease and other tauopathies.

Methods

To further elucidate how TTBK1/2 activity contributes to both TDP-43 and tau phosphorylation in the context

SUBMITTER: Taylor LM 

PROVIDER: S-EPMC5802059 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature