期刊论文详细信息
Neurobiology of Disease
Pre-assembled tau filaments phosphorylated by GSK-3b form large tangle-like structures
T. Chris Gamblin1  Qian Sun2  Carolyn A. Rankin2 
[1] Corresponding author. Fax: +1 785 864 5321.;Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA;
关键词: Tau;    Alzheimer's disease;    GSK-3β;    Phosphorylation;    Hyperphosphorylation;    Neurofibrillary tangle;   
DOI  :  
来源: DOAJ
【 摘 要 】

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-3β 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-associated antibodies. These tangle-like structures are optically visible and are similar to those formed by polymerization of GSK-3β phosphorylated tau monomer and to those isolated from Alzheimer's disease tissue. We conclude that the phosphorylation of tau by GSK-3β either prior to or following polymerization promotes polymer/polymer interactions that result in stable clusters of tau filaments.

【 授权许可】

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