＜Poster＞15-Deoxy-Δ^12,14-prostaglandin J_2 modifi es profi les of nuclear TDP-43 protein through its direct binding : Implication for the pathogenesis of TDP-43 proteinopathy

フォーマット:

論文

責任表示:

Zhang, Hai-xin ; Tanji, Kunikazu ; Yoshida, Hidemi ; Hayakari, Makoto ; Mori, Fumiaki ; Wakabayashi, Koichi

言語:

英語

出版情報:

弘前大学大学院医学研究科・弘前医学会, 2010-07-08

著者名:

Zhang, Hai-xin

Tanji, Kunikazu

Yoshida, Hidemi

Hayakari, Makoto

Mori, Fumiaki

Wakabayashi, Koichi

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掲載情報:

弘前医学

ISSN:

0439-1721      

巻:

61

通号:

Supplement

開始ページ:

S204

終了ページ:

S210

バージョン:

publisher

概要:

TDP-43 proteinopathy （amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions） is a newly categorized group of neurodegenerative disorders characterized by abnormal accumulation and mislocaliza … tion of nuclear TDP-43 protein in the neuronal cytoplasm. 15-deoxy-Δ12,14-prostaglandin J2 （15d-PGJ2） is non-enzymatically produced from PGD2, and plays roles in infl ammation and oxidative stress responses. Indeed, 15d-PGJ2 is up-regulated in the spinal motor neurons in ALS. In this study, biochemical and fluorescent staining analyses showed that 15d-PGJ2 modifi es expression, solubility, and subcellular localization of TDP-43. This alteration was at least partly related to a cyclopentenone ring structure containing an electrophilic carbon of 15d-PGJ2, because 15d-PGJ2 analogue, which lacks an cyclopentenone ring structure, had almost no eff ect on TDP-43 protein. Finally in vitro binding experiment indicated that 15d-PGJ2 is covalently bound to TDP-43 protein. These fi ndings suggest that a sustained high level of 15d-PGJ2 is involved in the pathogenesis of neurodegenerative disorders related to abnormal TDP-43 protein. 続きを見る

URL:

http://hdl.handle.net/10129/3689