臨床神経学

<シンポジウム29―2>脊髄小脳変性症update

脊髄小脳失調症(SCA31)の分子病態解明

石川 欽也1), 新美 祐介1), 佐藤 望1), 網野 猛志1)2), 水澤 英洋1)

1)東京医科歯科大学大学院脳神経病態学〔〒113―8519 東京都文京区湯島1―5―45〕
2)現 武蔵野赤十字病院神経内科

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/SCA 3, DRPLA, SCA 1 and SCA 2 are SCAs often associated with extracerebellar 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)n in vitro. Our preliminary data also demonstrated that (UGGAA)n is toxic when expressed in cultured cells. These findings may imply that RNAmediated pathogenesis is involved in SCA31. Further studies are needed to explore precise mechanism of this disease.
Full Text of this Article in Japanese PDF (384K)

(臨床神経, 51:1122−1124, 2011)
key words:脊髄小脳失調症,小脳,RNA介在型神経筋疾患,RNA結合蛋白,SCA31

(受付日:2011年5月20日)