- 著者
- 石川 欽也 新美 祐介 佐藤 望 網野 猛志 水澤 英洋
- 出版者
- 日本神経学会
- 雑誌
- 臨床神経学 (ISSN:0009918X)
- 巻号頁・発行日
- vol.51, no.11, pp.1122-1124, 2011 (Released:2012-01-24)
- 参考文献数
- 10
- 被引用文献数
- 1 1
Spinocerebellar ataxia is a group of neurodegenerative disorders clinically presenting adult onset cerebellar ataxia. To date, 21 different genes (SCA1, 2, 3, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 17, 23, 27, 28, 31, 35, 36 and DRPLA) and additionally 10 different gene loci (SCA4, 18, 19, 20, 21, 25, 26, 29, 30 and 32) are identified. Among these, SCA6 and SCA31 are the two common diseases clinically presenting as a relatively predominant cerebellar syndrome, whereas Machado-Joseph disease/SCA3, DRPLA, SCA1 and SCA2 are SCAs often associated with extra-cerebellar manifestations. SCA31 is a late-onset purely cerebellar ataxia caused by a complex pentanucleotide repeat containing (TGGAA)n lying in an intronic region shared by two genes, BEAN (brain expressed, associated with NEDD4) and TK2 (thymidine kinase 2). In situ hybridization analysis in patients' Purkinje cells demonstrated that pentanucleotide repeats transcribed in BEAN direction form RNA aggregates ("RNA foci"), and essential splicing factors, SFRS1 and SFRS9, bind to (UGGAA)n, the transcript of (TGGAA)nin vitro. Our preliminary data also demonstrated that (UGGAA)n is toxic when expressed in cultured cells. These findings may imply that RNA-mediated pathogenesis is involved in SCA31. Further studies are needed to explore precise mechanism of this disease.
1 0 0 0 OA 小脳疾患患者・マウスの運動力学解析に基づく姿勢機能障害の構成論的解明
小脳における神経障害が姿勢制御機能を低下するメカニズムを解明するために、生体データから力学モデルを用いて制御系を定量評価する手法を構築した。①環境に応じて運動状態を変える力学モデルとその評価手法、②後肢2足で直立するラットの姿勢実験環境という2つのツールの開発することで制御系の評価手法を構築し、この手法を用いて下オリーブ核障害ラット及び小脳疾患患者の制御系を評価することで、小脳障害が制御入力全体や環境適応のために働く制御機能を低下させるという姿勢制御能力の低下要因を示した。