Expression of N19S-SOD1, an SOD1 mutant found in sporadic amyotrophic lateral sclerosis patients, induces low-grade motoneuronal toxicity

Yuji Obata, Takako Niikura, Kohsuke Kanekura, Yuichi Hashimoto, Masaoki Kawasumi, Yoshiko Kita, Sadakazu Aiso, Masaaki Matsuoka, Ikuo Nishimoto

研究成果: Article査読

11 被引用数 (Scopus)

抄録

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease. It has been generally accepted that the proapoptotic property of the familial ALS (FALS)-linked mutant SOD1 genes plays an important role in the pathogenesis of some FALS cases. We found here that expression of N19S-SOD1, a novel SOD1 mutant originally found in a sporadic ALS patient, induces lower grade death in NSC34 cells than FALS-linked mutant SOD1. In agreement, intracytoplasmic aggregate formation and SOD1 polymerization are less prominently induced by ectopic expression of N19S-SOD1 than FALS-linked mutant SOD1. We further found that additional cell stresses, such as inhibition of proteasomal activity or up-regulation of intracellular oxidative stress, enhance N19S-SOD1-induced aggregate formation and polymerization of N19S-SOD1. Such analysis of the intracellular polymerization and the ubiquitination of N19S-SOD1 have further suggested that it is recognized as a misfolded protein, like FALS-linked mutant SOD1, whereas wild-type SOD1 is not. Altogether, it is speculated that the N19S mutation of SOD1 in cooperation with associated cell stresses contributes to the onset of ALS as a risk factor.

本文言語English
ページ(範囲)720-729
ページ数10
ジャーナルJournal of Neuroscience Research
81
5
DOI
出版ステータスPublished - 2005 9月 1
外部発表はい

ASJC Scopus subject areas

  • 細胞および分子神経科学

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