Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans

摘要: The paired helical filament (PHF) is the major component of neurofibrillary deposits that form a defining neuropathological characteristic Alzheimer's disease. PHFs are composed microtubule-associated protein tau, in hyperphosphorylated state. Hyperphosphorylation tau results its inability to bind microtubules and believed precede PHF assembly. However, it unclear whether hyperphosphorylation either necessary or sufficient for formation. Here we show non-phosphorylated recombinant isoforms with three microtubule-binding repeats helical-like filaments under physiological conditions vitro, when incubated sulphated glycosaminoglycans such as heparin heparan sulphate. Furthermore, prevents from binding promotes microtubule disassembly. Finally, sulphate coexist nerve cells disease brain at earliest known stages pathology. These findings, previous studies which stimulates phosphorylation by number kinases, indicate may be key factor formation lesions