title: Altered tubulin assembly dynamics with N-homocysteinylated human 4R/1N tau in vitro.
abstract: Tau isoforms promote neuronal integrity through binding and stabilization of microtubule proteins (MTP). It has been shown that hyperphosphorylation of tau contributes to Alzheimer's disease (AD) pathology and related tauopathies. However, other pathogenic modifications of tau have not been well characterized. It is well accepted that elevated level of homocysteine (Hcy) is associated with neurodegenerative diseases such as AD. As a result of N-homocysteinylation of lysine residues, Hcy becomes a component of proteins, as a protein-homocystamide adduct, which affects protein structure and function. Here we demonstrate that N-homocysteinylation of human tau (4R/1N isoform) inhibits its function via impaired tau-tubulin specific binding and MTP assembly dynamics in vitro.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Oveis
authors.initials: O
authors.lastname: Karima
authors.forename: Gholamhossein
authors.initials: G
authors.lastname: Riazi
authors.forename: Sirus
authors.initials: S
authors.lastname: Khodadadi
authors.forename: Hassan
authors.initials: H
authors.lastname: Aryapour
authors.forename: Mohammad Ali Nasiri
authors.initials: MA
authors.lastname: Khalili
authors.forename: Leila
authors.initials: L
authors.lastname: Yousefi
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Moosavi-Movahedi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D006710:Homocysteine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D020033:Protein Isoforms; D012996:Solutions; D014404:Tubulin; D016875:tau Proteins; D006710:Homocysteine