title: Probable participation of 14-3-3 in tau protein oligomerization and aggregation.
abstract: Aggregation of tau proteins followed by formation of paired helical filaments and neurofibrillary tangles is considered as a hallmark of certain neurodegenerative disorders such as different tauopathies and Alzheimer's disease (AD). Tau aggregation is dependent on the presence of polyanions, cellular redox state, limited proteolysis, and different posttranslational modifications among which tau phosphorylation plays a particularly important role. Although it is still debatable whether tau aggregation is harmful or protective for the cell, detailed analysis of molecular mechanisms underlying this process seems to be of great importance for understanding AD pathogenesis. This review is focused on universal adapter proteins 14-3-3 that seem to be significant partners to tau protein in neurons. 14-3-3 interacts with nonphosphorylated tau and promotes its interaction with and phosphorylation by a number of protein kinases. 14-3-3 induces aggregation of nonphosphorylated tau and does not affect aggregation of tau phosphorylated at specific sites. Due to its high concentration in neurons, 14-3-3 can compete with tubulin for interaction with tau. Binding to phosphorylated tau, 14-3-3 might inhibit its dephosphorylation by protein phosphatases and by this means indirectly affect interaction of tau with microtubules and tau aggregation. Finally, 14-3-3 might promote sequestration of dangerous small tau oligomers and stabilize tau aggregates. We propose that 14-3-3 should be considered an important participant of the complex process of tau aggregation and as a potential therapeutic target in treating AD.
authors.affiliation: Department of Biochemistry, School of Biology, Moscow State University, Moscow, Russian Federation.
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Sluchanko
authors.forename: Nikolai B
authors.initials: NB
authors.lastname: Gusev
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D016875:tau Proteins