title: Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS.
abstract: A monoclonal antibody specific for phosphoserines 409 and 410 of TDP-43 (mAb pS409/410) has been produced. It strongly stained TDP-43-positive inclusions in brain of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis, but did not stain nuclei, in which normal TDP-43 is localized. It did not recognize TDP-43 rapidly extracted from brains of rats at various developmental stages, strongly suggesting that phosphorylation of Ser409/410 is an abnormal event. Analysis of postmortem changes of TDP-43 revealed that the amounts of Sarkosyl-insoluble, urea-soluble full-length TDP-43 and a 35kDa N-terminal fragment increased time-dependently.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Inukai
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Arai
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Emanuele
authors.initials: E
authors.lastname: Buratti
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hisanaga
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D010768:Phosphoserine; D012694:Serine