Identification of a novel gene responsible for spinocerebellar ataxia and therapy for ataxia

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: IKEDA Yoshio 岡山大学, 岡山大学病院, 講師 (00282400)
• Co-Investigator(Kenkyū-buntansha): ABE Koji 岡山大学, 大学院・医歯薬学総合研究科, 教授 (20212540)
• Project Period (FY): 2009 – 2011
• Keywords: 脊髄小脳変性症 / ポジショナルクローニング / spinocerebellar ataxia / SCD / Asidan / SCA36 / NOP56 / GGCCTGリピート

Research Abstract

To reveal the molecular pathomechanism and identify a novel gene responsible for spinocerebellar ataxia, positional cloning of SCA families with unknown etiology was performed. A novel genetic defect causing characteristic clinical features with ataxia complicated by motor neuron involvement had been discovered from this study as a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene. The specific molecular effect of mutated transcripts might be related to RNA gain-of-function mechanism.

Research Products

• [Journal Article] Clinicoepidemiological analysis of genetic testing in 1, 000 cases of hereditary neurological disorders (2011)
  • Author(s): Kametaka S, Ikeda Y, Abe K
  • Journal Title: Rinsho Shinkeigaku Volume: 51 Pages: 471-7
  • Peer Reviewed
• [Journal Article] Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement (2011)
  • Author(s): Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A
  • Journal Title: Am J Hum Genet Volume: 89 Pages: 121-30
  • Peer Reviewed
• [Journal Article] Differential clinical features in a pair of monozygotic twins with dentatorubropallidoluysian atrophy (2011)
  • Author(s): Sato K, Yunoki T, Morimoto N, Nagotani S, Deguchi K, Takehisa Y, Ikeda Y, Matsuura T, Abe K, Yamamoto Y
  • Journal Title: Eur J Neurol Volume: 18 Pages: e100-1
  • Peer Reviewed
• [Journal Article] Correlation of cerebral spinal fluid pH and HCO3(-) with disease progression in ALS (2011)
  • Author(s): Morimoto N, Deguchi K, Sato K, Yunoki T, Deguchi S, Ohta Y, Kurata T, Takao Y, Ikeda Y, Matsuura T, Abe K
  • Journal Title: J Neurol Sci Volume: 307 Pages: 74-8
  • Peer Reviewed
• [Journal Article] Comparisons of acoustic function in SCA31 and other forms of ataxias (2011)
  • Author(s): Ikeda Y, Nagai M, Kurata T, Yamashita T, Ohta Y, Nagotani S, Deguchi K, Takehisa Y, Shiro Y, Matsuura T, Abe K
  • Journal Title: Neurol Res Volume: 33 Pages: 427-32
  • Peer Reviewed
• [Journal Article] Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α (2011)
  • Author(s): Kozuki M, Kurata T, Miyazaki K, Morimoto N, Ohta Y, Ikeda Y, Abe K
  • Journal Title: Brain Res Volume: 1388 Pages: 32-8
  • Peer Reviewed
• [Journal Article] Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis (2011)
  • Author(s): Miyazaki K, Ohta Y, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Abe K
  • Journal Title: J Neurosci Res Volume: 89 Pages: 718-28
  • Peer Reviewed
• [Journal Article] Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice (2011)
  • Author(s): Kurata T, Miyazaki K, Kozuki M, Violeta-Lukic-Panin, Morimoto N, Ohta Y, Nagai M, Ikeda Y, Matsuura T, Abe K
  • Journal Title: Brain Res Volume: 1371 Pages: 161-70
  • Peer Reviewed
• [Journal Article] Prevalence of autosomal dominant cerebellar ataxia in Ao mori, the northernmost prefecture of Honshu, Japan (2010)
  • Author(s): Yamamoto-Watanabe Y, Watanabe M, Hikichi M, Ikeda Y, Jackson M, Wakasaya Y, Matsubara E, Kawarabayashi T, Kannari K, Shoji M
  • Journal Title: Intern Med Volume: 49 Pages: 2409-2414
  • Peer Reviewed
• [Journal Article] A Japanese ALS6 family with mutation R521C in the FUS/TLS gene : a clinical, pathological and genetic report (2010)
  • Author(s): Yamamoto-Watanabe Y, Watanabe M, Okamoto K, Fujita Y, Jackson M, Ikeda M, Nakazato Y, Ikeda Y, Matsubara E, Kawarabayashi T, Shoji M
  • Journal Title: J Neurol Sci Volume: 296 Pages: 59-63
  • Peer Reviewed
• [Journal Article] Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene (2010)
  • Author(s): Morimoto N, Nagai M, Miyazaki K, Ohta Y, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Asanuma M, Abe K
  • Journal Title: J Neurosci Res Volume: 88 Pages: 1804-1811
  • Peer Reviewed
• [Journal Article] Familial amyloid polyneuropathy(Finnish type) presenting multiple cranial nerve deficits with carpal tunnel syndrome and orthostatic hypotension (2010)
  • Author(s): Makioka K, Ikeda M, Ikeda Y, Nakasone A, Osawa T, Sasaki A, Otani T, Arai M, Okamoto K
  • Journal Title: Neurol Res Volume: 32 Pages: 472-475
  • Peer Reviewed
• [Journal Article] Spinal anterior horn has the capacity to self-regenerate in amyotrophic lateral sclerosis model mice (2009)
  • Author(s): Miyazaki K, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Abe K
  • Journal Title: J Neurosci Res Volume: 87 Pages: 3639-3648
  • Peer Reviewed
• [Journal Article] RNA gain-of-function in spinocerebellar ataxia type 8 (2009)
  • Author(s): Daughters RS, Tuttle DL, Gao W, Ikeda Y, Moseley ML, Ebner TJ, Swanson MS, Ranum LP
  • Journal Title: PLoS Genet Volume: 5 Pages: e1000600
  • Peer Reviewed
• [Journal Article] Changes of Nogo-A and receptor NgR in the lumbar spinal cord of ALS model mice (2009)
  • Author(s): Miyazaki K, Nagai M, Ohta Y, Morimoto N, Kurata T, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K
  • Journal Title: Neurol Res Volume: 31 Pages: 316-321
  • Peer Reviewed
• [Presentation] SCA31および他の小脳失調症における聴覚障害の検討 (2011)
  • Author(s): 池田佳生、倉田智子、山下徹、太田康之、出口章子、出口健太郎、武久康、城洋志彦、松浦徹、阿部康二
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 20110518-20
• [Presentation] 岡山大学神経内科における遺伝子検査1, 000件の臨床疫学的解析 (2011)
  • Author(s): 亀高さつき、池田佳生、阿部康二
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 20110518-20
• [Presentation] 運動失調症の治療開発研究への応用をめざした上肢協調運動障害の数量化測定装置の開発 (2010)
  • Author(s): 池田佳生、辻徳生、折戸謙介、松浦徹、石井抱、阿部康二
  • Organizer: 第28回日本神経治療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20100715-16
• [Presentation] SCDにおける上肢協調運動障害の数量化測定装置の開発 (2009)
  • Author(s): 池田佳生、宮崎一徳、森本展年、倉田智子、永井真貴子、武久康、辻徳生、折戸謙介、石井抱、阿部康二
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 20090520-22
• [Presentation] 歯状核赤核淡蒼球ルイ体萎縮症(DRPLA)の一卵性双生児例についての検討 (2009)
  • Author(s): 佐藤恒太、柚木太淳、森本展年、名古谷章子、出口健太郎、永井真貴子、武久康、池田佳生、松浦徹、阿部康二
  • Organizer: 第87回日本神経学会中国・四国地方会
  • Place of Presentation: 高松
  • Year and Date: 2009-12-05
• [Remarks] 岡山大学神経内科ホームページ
  • URL: http://www.okayama-u.ac.jp/user/med/shinkeinaika