Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS.
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.
Inukai
Yuki
Y
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Nonaka
Takashi
T
Arai
Tetsuaki
T
Yoshida
Mari
M
Hashizume
Yoshio
Y
Beach
Thomas G
TG
Buratti
Emanuele
E
Baralle
Francisco E
FE
Akiyama
Haruhiko
H
Hisanaga
Shin-ichi
S
Hasegawa
Masato
M
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*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D010768:Phosphoserine; D012694:Serine