Cleavage of human tau at Asp421 inhibits hyperphosphorylated tau induced pathology in a Drosophila model.

ABSTRACT: Hyperphosphorylated and truncated tau variants are enriched in neuropathological aggregates in diseases known as tauopathies. However, whether the interaction of these posttranslational modifications affects tau toxicity as a whole remains unresolved. By expressing human tau with disease-related Ser/Thr residues to simulate hyperphosphorylation, we show that despite severe neurodegeneration in full-length tau, with the truncation at Asp421, the toxicity is ameliorated. Cytological and biochemical analyses reveal that hyperphosphorylated full-length tau distributes in the soma, the axon, and the axonal terminal without evident distinction, whereas the Asp421-truncated version is mostly restricted from the axonal terminal. This discrepancy is correlated with the fact that fly expressing hype

SUBMITTER: Chi H 

PROVIDER: S-EPMC7417559 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature