Pre-assembled tau filaments phosphorylated by GSK-3b form large tangle-like structures.

ABSTRACT: Hyperphosphorylated tau protein is a major component of neurofibrillary tangles, a prominent intracellular hallmark of Alzheimer's disease. Both hyperphosphorylated tau and neurofibrillary tangles have been shown to correlate with dementia in Alzheimer's disease, but the relationship between hyperphosphorylation and tangle formation is not clear. Using a cell-free in vitro model system, in which tau polymerization is induced by arachidonic acid, we show that GSK-3beta phosphorylation of pre-assembled tau filaments makes those filaments prone to coalesce into large neurofibrillary tangle-like structures. Five phosphorylation sites, S199, T205, T231, S396 and S404, were identified in the phosphorylated filaments; many of the five are within epitopes recognized by Alzheimer's disease-associat

SUBMITTER: Rankin CA 

PROVIDER: S-EPMC2607042 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature