＜シンポジウム35―3＞運動ニューロン疾患の分子病態の解明と治療開発への展望
ALSにおける軸索輸送の役割
―dynactin-1を標的とした孤発性ALSモデルの開発―
田中 章景, 池中 建介, 祖父江 元
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〕
Proposed hypothesis for pathomechanisms of sporadic ALS include oxidative stress, glutamate toxicity, axonal transport defects, mitochondrial impairment and so on. Although these mechanisms may be interrelated mutually, the whole picture has not been clarified. As for axonal transport defect, it is also prominently involved in the pathogenesis of many major human neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, suggesting a crucial role of axonal transport in maintaining the normal neuronal function. In mutant SOD1 transgenic mice, the most popular disease model of familial ALS, the mutant SOD1 selectively associates with and damages mitochondria, leading to defect of axonal transport because of diminished ATP fuel supply for the molecular motors such as kinesin family or dynein/dynactin complex. Furthermore, the finding that mutations in the dynactin subunit p150Glued cause familial ALS demonstrates a direct role of molecular motor dysfunction and axonal transport defects in ALS. On the other hand, the mechanism of axonal transport impairment in sporadic ALS has been elusive. We have previously demonstrated that gene expression of dynactin subunit p150Glued (dynactin-1) is down-regulated in motor neurons of sporadic ALS patient from the early stage of neurodegeneration. In this article we review the role of axonal transport in the pathogenesis of ALS.
Full Text of this Article in Japanese PDF (203K)
(臨床神経, 51：1189−1191, 2011)
key words：筋萎縮性側索硬化症，軸索輸送，ダイナクチン-1，疾患モデル
（受付日：2011年5月20日）
