Mechanism of motor neuron death in ALS: transcription activity of ribosomal RNA gene and TDP-43

2012 Fiscal Year Final Research Report

• Project/Area Number: 22300117
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Shinshu University
• Principal Investigator: OYANAGI Kiyomitsu 信州大学, 医学部, 教授 (00134958)
• Co-Investigator(Kenkyū-buntansha): MIZUTANI Toshio 公益財団法人東京都医学総合研究所, 東京都神経科学総合研究所, 研究員 (40124416) ; YAMAZAKI Mineo 日本医科大学, 医学部, 准教授 (10277577)
• Project Period (FY): 2010 – 2012
• Keywords: 神経変性疾患

Research Abstract

The present study elucidate the abnormalities in the protein synthesis system in the motor neurons in the spinal cords in patients with amyotrophic lateral sclerosis (ALS). Those abnormalities are as follows: 1) decrease of ribosomal (r) RNA gene transcription activity, 2) correlation between rRNA gene activity and amount of nucleolin in the nucleus, 3) aggregation of the molecular chaperone, and 4) seeding each other in aggregation of molecular chaperone and cystatin C, which is a component of the Bunina body.

Research Products

• [Journal Article] Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. (2013)
  • Author(s): Takahashi T, Aoki M, Suzuki N, Tateyama M, Yaginuma C, Sato H, Hayasaka M, Sugawara H, Ito M, Abe-Kondo E, Shimakura N, Ibi T, Kuru S, Wakayama T, Sobue G, Fujii N, Saito T, Matsumura T, Funakawa I, Mukai E, Kawanami T, Morita M, Yamazaki M, Hasegawa T, Shimizu J, Tsuji S, Kuzuhara S, Tanaka H, Yoshioka M, Konno H, Onodera H, Itoyama Y
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84 Pages: 433-440
  • DOI: DOI:10.1136/jnnp-2011-301339
  • Peer Reviewed
• [Journal Article] Supranuclear ophthalmoparesis and vacuolar degeneration of the cerebral white matter in amyotrophic lateral sclerosis: a clinicopathologic study (2012)
  • Author(s): Takeda T, Uchihara T, Mochizuki Y, Ishihara A, Nakamura A, Sasaki S, Uchiyama S, Iwata M, Mizutani T
  • Journal Title: Amyotrophic lateral sclerosis Volume: 13 Pages: 74-86
  • DOI: DOI:10.3109/17482968.2011.603731
  • Peer Reviewed
• [Journal Article] 中枢神経の所見の取り方 1. 一般的な見方、切り出し (2012)
  • Author(s): 橋本智代,小柳清光
  • Journal Title: 病理と臨床 Volume: 30 Pages: 149-157
• [Journal Article] Hereditary diffuse leukoencephalopathy with axonal spheroids caused by R782H mutation in CSF1R: Case report (2012)
  • Author(s): Kinoshita M, Yoshida K, Oyanagi K, Hashimoto T, Ikeda S
  • Journal Title: Journal of the Neurological Sciences Volume: 318 Pages: 115-118
  • DOI: DOI:10.1016/j.jns.2012.03.012
  • Peer Reviewed
• [Journal Article] Distinctive clinicopathological features of 2 large families with amyotrophic lateral sclerosis having L106V mutation in SOD1 gene. (2012)
  • Author(s): Hineno A, Nakamura A, Shimojima Y, Yoshida K, Oyanagi K, Ikeda S
  • Journal Title: Journal of the Neurological Sciences Volume: 319 Pages: 63-74
  • DOI: DOI:10.1016/j.jns.2012.05.014
  • Peer Reviewed
• [Journal Article] Familial ALS with FUS P525L mutation: two Japanese sisters with multiple system involvement. (2012)
  • Author(s): Mochizuki Y, Isozaki E, Takao M, Hashimoto T, Shibuya M, Arai M, Hosokawa M, Kawata A, Oyanagi K, Mihara B, Mizutani T
  • Journal Title: Journal of the Neurological Sciences Volume: 323 Pages: 85-92
  • DOI: DOI:10.1016/j.jns.2012.08.016.
  • Peer Reviewed
• [Journal Article] TDP-43 と筋萎縮性側索硬化症(ALS)・前頭側頭葉変性症(FTLD)の神経細胞死 (2011)
  • Author(s): 小柳清光、橋本智代
  • Journal Title: 信州医学雑誌 Volume: 59 Pages: 63-72
• [Journal Article] Radiologic and neuropathologic findings in patients in a pedigree with dentatoruburalpallidoluysian atrophy (2011)
  • Author(s): Sunami Y, Koide R, Ara, N, Yamada M, Mizutani T, Oyanagi K
  • Journal Title: American Journal of Neuroradiology Volume: 32 Pages: 109-114
  • DOI: DOI:10.3174/ajnr.A2252.
  • Peer Reviewed
• [Journal Article] Temporary focal cerebral ischemia results in swollen astrocytic end-feet that compress microvessels and lead to focal cortical infarction (2011)
  • Author(s): Ito U, Hakamata Y, Kawakami E, Oyanagi K
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism Volume: 31 Pages: 328-338
  • DOI: DOI:10.1038/jcbfm.2010.97.
  • Peer Reviewed
• [Journal Article] Survival motor neuron (SMN) protein in the spinal anterior horn cells of patients with sporadic amyotrophic lateral sclerosis (2011)
  • Author(s): Piao Y, Hashimoto T, Takahama S, Kakita A, Komori T, Morita T, Takahashi H, Mizutani, T, Oyanagi K
  • Journal Title: Brain Research Volume: 1372 Pages: 152-159
  • DOI: DOI:10.1016/j.brainres.2010.11.070.
  • Peer Reviewed
• [Journal Article] 神経病理入門. I. 基本的な脳標本の作製法 (2011)
  • Author(s): 橋本智代、 小柳清光
  • Journal Title: Medical Technology Volume: 39 Pages: 939-946
• [Journal Article] 先行感染後に発症した抗 AQP4 抗体陽性の視神経脊髄炎84 歳男性剖検例. (2011)
  • Author(s): 佐藤俊一、星 研一、渡辺正秀、日根野晃代、小柳清光、矢彦沢裕之
  • Journal Title: 臨床神経 Volume: 51 Pages: 583-589
  • Peer Reviewed
• [Journal Article] Electrophysiological assessment of corticorespiratory pathway function in amyotrophic lateral sclerosis. (2010)
  • Author(s): Shimizu T, Komori T, Kugio Y, Fujimaki Y, Oyanagi K, Hayashi H
  • Journal Title: Amyotrophic Lateral Sclerosis Volume: 11 Pages: 57-62
  • DOI: DOI:10.1080/17482960903207385
  • Peer Reviewed
• [Journal Article] アム島の筋萎縮性側索硬化症(ALS) -TDP-43 と神経原線維変化から見るパーキンソン認知症、古典型 ALS,」前頭側頭葉変性症との異同-. (2010)
  • Author(s): 小柳清光、橋本智代、山崎峰雄
  • Journal Title: 最新医学 Volume: 65 Pages: 1632-1641
• [Presentation] Usability of biosignal communication devices for patients with amyotrophic lateral sclerosis (ALS) using tracheostomy ventilation (2012)
  • Author(s): Nakayama Y, Matsuda C, Oyanagi K, et al.
  • Organizer: The 24th Annual International Symposium on ALS/MND.
  • Place of Presentation: 米国 Chicago
  • Year and Date: 2012-12-05
• [Presentation] 構音障害、運動失調、認知症状を呈し、クラーク柱神経細胞脱落とレビ-小体とを呈したポリグルタミン封入体陽性 85 歳例 (2012)
  • Author(s): 小柳清光、吉田邦広、他
  • Organizer: 第53回日本神経病理学会
  • Place of Presentation: 新潟市
  • Year and Date: 2012-06-30
• [Presentation] 上位運動ニューロンの組織変性が下位のそれに比し高度であった ALS 剖検例の検討. (2012)
  • Author(s): 他田真理、小柳清光、高橋均、他
  • Organizer: 第53回日本神経病理学会
  • Place of Presentation: 新潟市
  • Year and Date: 2012-06-30
• [Presentation] SOD1 遺伝子 L106V 変異家族性筋萎縮性側索硬化症におけるユビキチン関連蛋白の免疫組織学的検討. (2012)
  • Author(s): 日根野晃代、小柳清光、他
  • Organizer: 第53回日本神経病理学会
  • Place of Presentation: 新潟市
  • Year and Date: 2012-06-29
• [Presentation] 口咽頭部・頸部・上肢近位部に限局する筋萎縮性側索硬化症(ALS)の 1 剖検例 (2012)
  • Author(s): 三上裕嗣、尾野精一、 小柳清光、他
  • Organizer: 第53回日本神経病理学会
  • Place of Presentation: 新潟市
  • Year and Date: 2012-06-29
• [Presentation] 孤発性筋萎縮性側索硬化症(ALS)の初期病変-全経過 6 ヶ月の 1 剖検例. (2012)
  • Author(s): 安井香奈子、尾野精一、小柳清光、他:
  • Organizer: 第53回日本神経病理学会
  • Place of Presentation: 新潟市
  • Year and Date: 2012-06-29
• [Presentation] 頻発する SOD1 遺伝子 L106V変異家系における責任病巣. (2012)
  • Author(s): 日根野晃代、小柳清光、他: ALS の神経因性膀胱
  • Organizer: 第53回日本神経学会
  • Place of Presentation: 東京都
  • Year and Date: 2012-05-23
• [Presentation] Distinct clinicopathological features in two large families with familial amyotrophic lateral sclerosis having L106V mutation in the copper/zinc superoxide dismutase (SOD1) gene. (2011)
  • Author(s): Hineno A, Nakamura A, Shimojima Y, Yoshida K, Oyanagai K, Ikeda S
  • Organizer: 第2回アジア神経病理学会
  • Place of Presentation: 北京. 中国
  • Year and Date: 2011-11-05
• [Presentation] 認知症を呈した成人発症常染色体優性遺伝性の神経軸索ジストロフィーの脳生検例 (2011)
  • Author(s): 小柳清光、矢彦沢裕之、他
  • Organizer: 第52回日本神経病理学会
  • Place of Presentation: 京都市
  • Year and Date: 2011-06-04
• [Book] Magnesium in Parkinson's Disease: an update in clinical and basic aspects (2011)
  • Author(s): Oyanagi K, Hashimoto T
  • Total Pages: 229-236
  • Publisher: In: Magnesium in the Central Nervous System (Eds: Vink B, Nechifor M) Unversity of Adelaide Press, Adelaide
• [Book] Parkinsonism-dementia complex (2011)
  • Author(s): Oyanagi K, Hashimoto T, Yamazaki M
  • Total Pages: 171-178
  • Publisher: In: Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders (Eds: Weller RO, Dickson DW) Springer, Oxford
• [Remarks]
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/department/medical_science/course/course35.html