title: Transition of tau protein from disordered to misordered in Alzheimer's disease.
abstract: The neuronal protein tau, a member of the class of intrinsically disordered proteins, is characterized by the absence of any firm 3-D structure and high solubility when free in solution. The tau protein forms insoluble fibrils in the brain of people suffering from Alzheimer's disease (AD) and other tauopathies and plays a key role in the neurodegenerative process. Posttranslational events leading to the transition of tau from a disordered highly soluble protein to the insoluble aggregate seem to be associated with hyperphosphorylation, truncation or a combination of both. These modifications are assumed to change the native disorder of tau into a preaggregation state, which then directly initiates the fibrillization process. Conformation-specific anti-tau antibody DC11 detects pathological truncated tau forms present in AD brains but not in the normal human brain. A truncated tau protein selected from this pool of DC11-positive molecules was sufficient to initiate and drive the complete tau cascade of neurofibrillary pathology in a rat model of tauopathy. Thus, DC11 antibody recognizes the AD-specific conformation of tau not found in the normal human brain. We propose the term 'misdisordered' for this distinct conformational state of tau, which is the first step in the transition of tau from a soluble disordered protein to its insoluble, misordered aggregated form.
authors.affiliation: Institute of Neuroimmunology, AD Centre, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Branislav
authors.initials: B
authors.lastname: Kovacech
authors.forename: Rostislav
authors.initials: R
authors.lastname: Skrabana
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D011487:Protein Conformation; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins