title: Biochemistry and cell biology of tau protein in neurofibrillary degeneration.
abstract: Tau represents the subunit protein of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications (phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming β structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.
authors: Max-Planck Unit for Structural Molecular Biology, c/o DESY, 22607 Hamburg, Germany; DZNE, German Center for Neurodegenerative Diseases, and CAESAR Research Center, 53175 Bonn, Germany. mandelkow@mpasmb.desy.de
authors: Eva-Maria
authors: EM
authors: Mandelkow
authors: Eckhard
authors: E
authors: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D006801:Humans; D008870:Microtubules; D009410:Nerve Degeneration / Q000378:metabolism*; D016874:Neurofibrillary Tangles; D009474:Neurons / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D016875:tau Proteins