title: Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau.
abstract: Alzheimer's disease-like neurofibrillary pathology is neither seen in rodents nor in transgenic animals expressing the disease causing mutant human APP or mutant human presenilins. Whether the absence of this pathology is due to inability of the murine tau to self assemble into filaments or due to some other factors is not understood. In this study, we compared recombinant murine and human taus in their ability to form filaments by AD-like hyperphosphorylation in vitro. Human and murine taus, 0N4R, were generated as recombinant proteins and phosphorylated with rat brain extract as a source of protein kinases. We found that murine tau could be hyperphosphorylated to similar stoichiometry and manner as human tau. Upon hyperphosphorylation, murine tau was able to self polymerize into bundles of paired helical filament- and straight filament-like morphology. The filaments obtained from self assembly of murine tau closely resembled those formed from identically treated human tau. Moreover, like human tau, 60-70% of murine tau aggregated on hyperphosphorylation.
authors.affiliation: Department of Neurochemistry, NYS Institute for Basic Research, Staten Island, NY 10314, USA.
authors.forename: M O
authors.initials: MO
authors.lastname: Chohan
authors.forename: N
authors.initials: N
authors.lastname: Haque
authors.forename: A
authors.initials: A
authors.lastname: Alonso
authors.forename: E
authors.initials: E
authors.lastname: El-Akkad
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: A
authors.initials: A
authors.lastname: Grover
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology*; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010766:Phosphorylation; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013045:Species Specificity; D016875:tau Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics
chemical_list: D011108:Polymers; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D016875:tau Proteins