Phosphorylated, but not native, tau protein assembles following reaction with the lipid peroxidation product, 4-hydroxy-2-nonenal

A correlation between hyperphosphorylation of tau protein and its aberrant assembly into paired helical filaments has lead to suggestions that phospho rylation controls assembly, but lacked a mechanistic basic. In this work, w e have found that phosphorylated, but not native, tau protein is able to fo rm polymers after the reaction with 4-hydroxy-2-nonenal, a highly toxic pro duct of lipid peroxidation. Phosphorylation of tau by both proline or non-p roline directed kinases, mas able to assemble it into polymers. (C) 2000 Fe deration of European Biochemical Societies. Published by Elsevier Science B .V. All rights reserved.