＜Symposium III＞Nubopathies : NUB1-related neurodegenerative diseases

フォーマット:

論文

責任表示:

Tanji, Kunikazu ; 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:

• Tanji, Kunikazu
• Mori, Fumiaki
• Wakabayashi, Koichi

掲載情報:

弘前医学

ISSN:

0439-1721      

巻:

61

通号:

Supplement

開始ページ:

S89

終了ページ:

S96

バージョン:

publisher

概要:

NEDD8 ultimate buster-1 （NUB1） is a potent down-regulator of the ubiquitin-like protein NEDD8, because it directly interacts with NEDD8 and targets it and its conjugates to the 26S proteasome for proteolytic degradation. Recently, we found … that NUB1 physically interacts with synphilin-1 through its NEDD8-binding site, implying that NUB1 also targets synphilin-1 to the 26S proteasome for proteolytic degradation. Synphilin-1 is an α-synuclein-interacting protein and is a major component of inclusion bodies found in the brains of patients with neurodegenerative α-synucleinopathies, including Parkinson’s disease. In our recent studies, we immunostained sections of brains from patients with Parkinson’s disease and other α-synucleinopathies and demonstrated that NUB1, as well as synphilin-1, accumulates in the inclusion bodies. To defi ne the role of NUB1 in the formation of these inclusion bodies, we performed a co-transfection assay using cultured HEK293 cells. This assay showed that NUB1 suppresses the formation of synphilin-1-positive inclusions. Further biochemical assays revealed that NUB1 overexpression leads to the proteasomal degradation of synphilin-1. These results and our previous observations suggest that NUB1 indeed targets synphilin-1 to the proteasome for its effi cient degradation, which, because of the resultant reduction in synphilin-1, suppresses the formation of synphilin-1-positive inclusions. In addition to these basic science aspects, our fi ndings on NUB1 have two important bearings clinically. First, they suggest that NUB1 could serve as a neuropathological marker in patients with α-synucleinopathies because it is strongly accumulated with synphilin-1 in the inclusions of their brain cells. Second, they suggest that NUB1 could be a potential therapeutic target for α-synucleinopathies. 続きを見る

URL:

http://hdl.handle.net/10129/3674