Abnormal phosphorylation of ser409/410 of TDP-43 in FTLD-U and ALS

被引：156

作者：

Inukai, Yuki ^{[1
,2
]}

Nonaka, Takashi ^{[1
]}

Arai, Tetsuaki ^{[3
]}

Yoshida, Mari ^{[4
]}

Hashizume, Yoshio ^{[4
]}

Beach, Thomas G. ^{[5
]}

Buratti, Emanuele ^{[6
]}

Baralle, Francisco E. ^{[6
]}

Akiyama, Haruhiko ^{[3
]}

Hisanaga, Shin-ichi ^{[2
]}

Hasegawa, Masato ^{[1
]}

机构：

[1] Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat, Dept Mol Neurobiol, Setagaya Ku, Tokyo 1568585, Japan

[2] Tokyo Metropolitan Univ, Grad Sch Sci, Mol Neurosci Lab, Tokyo 1920397, Japan

[3] Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat, Dept Psychogeriatr, Setagaya Ku, Tokyo 1568585, Japan

[4] Aichi Med Univ, Inst Med Sci Aging, Dept Neuropathol, Aichi 4801195, Japan

[5] Sun Hlth Res Inst, Sun City, AZ 85372 USA

[6] Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy

来源：

FEBS LETTERS | 2008年 / 582卷 / 19期

关键词：

ubiquitin; inclusions; tau; alpha-synuclein; degradation; aggregation;

D O I：

10.1016/j.febslet.2008.07.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 35 kDa N-terminal fragment increased time-dependently. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：2899 / 2904

页数：6

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