TBK1 suppresses mutant HTT induced toxicity and pathology in models of Huntington's disease

ABSTRACT: Phosphorylation of the N-terminal domain of the Huntingtin (HTT) protein has emerged as an important regulator of its localization, structure, aggregation, clearance, and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and assessing the therapeutic potential of targeting phosphorylation for the treatment of Huntington's Disease (HD) require the identification of the enzymes that regulate HTT phosphorylation. Herein, we report the discovery and validation of a kinase, TANK-binding kinase 1 (TBK1), that efficiently phosphorylates full-length and N-terminal HTT fragments in vitro (at S13/S16), in cells (at S13) and in vivo. TBK1 expression in HD models (cells, primary neurons, and C. elegans) increases mutant HTT exon 1 phosphorylation, reduces its aggregation

SUBMITTER: Dr. Ramanath, Narayana Hegde 

PROVIDER: S-SCDT-EMBOJ-2020-104671 | biostudies-other |

REPOSITORIES: biostudies-other