Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease.

ABSTRACT: Lafora progressive myoclonous epilepsy (Lafora disease; LD) is caused by mutations in the EPM2A gene encoding a dual specificity protein phosphatase named laforin. Our analyses on the Epm2a gene knock-out mice, which developed most of the symptoms of LD, reveal the presence of hyperphosphorylated Tau protein (Ser(396) and Ser(202)) as neurofibrillary tangles (NFTs) in the brain. Intriguingly, NFTs were also observed in the skeletal muscle tissues of the knock-out mice. The hyperphosphorylation of Tau was associated with increased levels of the active form of GSK3 beta. The observations on Tau protein were replicated in cell lines using laforin overexpression and knockdown approaches. We also show here that laforin and Tau proteins physically interact and that the interaction was limited to

SUBMITTER: Puri R 

PROVIDER: S-EPMC2755673 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature