臨床神経学

第49回日本神経学会総会

<シンポジウム7-2>ALSの研究・治療はどこまできたか
孤発性ALS病態関連分子の探索と疾患モデルの開発

田中 章景1), 和座 雅浩1), 丹羽 淳一2), 山本 正彦3), 祖父江 元1)

1)名古屋大学大学院医学系研究科・神経内科学〔〒466-8550 名古屋市昭和区鶴舞町65〕
2)愛知医科大学・神経内科
3)愛知学院大学心身科学部健康学科

The mechanism underlying the characteristic selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) has remained elusive. Modest advances in this research field have been achieved by the identification of copper/zinc superoxide dismutase 1 (SOD1) as one of the causative genes for rare familial ALS and by the development and analysis of mutant SOD1 transgenic animal models. However, in sporadic ALS (SALS) with many more patients, causative or critical genes situated upstream of the disease pathway have not yet been elucidated and no available disease models have been established. We have been working on screening these genes employing and combining several new technologies such as cDNA microarray, molecular indexing, and laser capture microdissection. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of SALS. Of these, in this paper, we will focus on Dorfin, a RING finger-type E3 ubiquitin ligase and dynactin1, a major component of dynein/dynactin complex that is important for retrograde axonal transport. We are now challenging creation of the disease models by simulating the gene expression changes specifically observed in SALS patients.
Full Text of this Article in Japanese PDF (278K)

(臨床神経, 48:970−972, 2008)
key words:孤発性筋萎縮性側索硬化症, 遺伝子発現解析, 疾患モデル, ドルフィン, ダイナクチン1

(受付日:2008年5月17日)