新たな神経変性疾患のバイオマーカーとしてのｍｉｃｒｏＲＮＡ

• 研究課題/領域番号: 24659423
• 研究種目: 挑戦的萌芽研究
• 配分区分: 補助金
• 研究分野: 神経内科学
• 研究機関: 東北大学
• 研究代表者: 武田 篤 東北大学, 医学(系)研究科(研究院), 非常勤講師 (70261534)
• 研究期間 (年度): 2012-04-01 – 2014-03-31
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 3,640千円 (直接経費: 2,800千円、間接経費: 840千円); 2013年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円); 2012年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
• キーワード: パーキンソン病 / バイオマーカー / シヌクレイノパチー / miRNA / 多系統萎縮症 / エクソソーム / 髄液

研究概要

パーキンソン病（PD）の髄液中エクソソームに含有されるmiRNAの解析を行った。対照3例およびPD5例の新鮮髄液10mlをAgilent社のmiRBase ver19.0で網羅的解析したところ、対照に対し有意に発現増加・減少がみられたmiRNAを複数得た。次いで、これらのmiRNAがターゲットとする遺伝子を解析したところ、miR-1xxxがTargetScan, miRDB, DIANA LABの3種の解析アルゴリズムで同一の遺伝子を標的とすることが判明した。この遺伝子はαシヌクレインの翻訳後修飾において極めて重要な役割を果たす事が知られており、PDの分子病態との関連が考えられた。

研究成果

• [雑誌論文] Cognitive impairment in multiple system atrophy : A position statement by the Neuropsychology Task Force of the MDS multiple system atrophy (MODIMSA) Study Group (2014)
  • 著者名/発表者名: Stankovic I., Krismer F., Jesic A., Antonini A., Benke T., Brown RG., Burn DJ., Holton JL., Kaufmann H., Kostic VS., Ling H., Meissner WG., Poewe W., Semnic M., Seppi K., Takeda A., Weintraub D., Wenning GK.
  • 雑誌名: Movement Disorders 巻: (in press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24753321
  • 査読あり
• [雑誌論文] Olfactory dysfunction and dementia in Parkinson's disease (2014)
  • 著者名/発表者名: Takeda A., Baba T., Kikuchi A., Hasegawa T., Sugeno N., Konno M., Miura E., Mori E.
  • 雑誌名: J. Parkinsons Dis 巻: (in press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24625830
  • 査読あり
• [雑誌論文] Pathogenesis of Multiple system atrophy. (2013)
  • 著者名/発表者名: Hasegawa T, Kikuchi A, Takeda A.
  • 雑誌名: Neurol Clin Neurosci 巻: 1 (6) 号: 6 ページ: 189-194
  • DOI: 10.1111/ncn3.57
  • 査読あり
• [雑誌論文] Hypometabolism in the supplementary and anterior cingulate cortices is related to dysphagia in Parkinson's disease: a cross-sectional and 3-year longitudinal cohort study (2013)
  • 著者名/発表者名: Akio Kikuchi, Toru Baba, Takafumi Hasegawa, Michiko Kobayashi, Naoto Sugeno, Masatoshi Konno, Emiko Miura, Yoshiyuki Hosokai, Toshiyuki Ishioka, Yoshiyuki Nishio, Kazumi Hirayama, Kyoko Suzuki, Masashi Aoki, ShokiTakahashi, Hiroshi Fukuda, Yasuto Itoyama, Etsuro Mori, Atsushi Takeda
  • 雑誌名: BMJ Open 巻: 3 号: 3 ページ: e002249-e002249
  • DOI: 10.1136/bmjopen-2012-002249
  • 査読あり
• [雑誌論文] Anti-voltage-gated potassium channel antibody is associated with chronic autonomic and sensory neuropathy. (2013)
  • 著者名/発表者名: Kaneko K, Tano O, Kikuchi A, Hasegawa T, Tateyama M, Yoshioka M, Saito H, Watanabe O, Takeda A, Aoki M.
  • 雑誌名: J Neurol 巻: 260 号: 1 ページ: 315-317
  • DOI: 10.1007/s00415-012-6730-0
  • 査読あり
• [雑誌論文] Suppression of dynamin GTPase decreases alpha-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy. (2012)
  • 著者名/発表者名: Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, Kikuchi A, Fiesel FC, Sasaki T, Aoki M, Itoyama Y, Takeda A.
  • 雑誌名: Mol Neurodegener 巻: 7 号: 1 ページ: 38-38
  • DOI: 10.1186/1750-1326-7-38
  • 査読あり
• [雑誌論文] Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia (2012)
  • 著者名/発表者名: Hiraoka K, Okamura N, Funaki Y, Hayashi A, Tashiro M, Hisanaga K, Fujii T, Takeda A, Y anai K, Iwata R, Mori E
  • 雑誌名: Eur Neurol 巻: 68 号: 3 ページ: 137-143
  • DOI: 10.1159/000338774
  • 査読あり
• [雑誌論文] Attentional Set-Shifting Deficit in Parkinson's Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study (2012)
  • 著者名/発表者名: Yoichi Sawada, Yoshiyuki Nishio, Kyoko Suzuki, Kazumi Hirayama, Atsushi Takeda, Yoshiyuki Hosokai, Toshiyuki Ishioka, Yasuto Itoyama, Shoki Takahashi, Hiroshi Fukuda, Etsuro Mori
  • 雑誌名: PLoS ONE 巻: 7(6) 号: 6 ページ: e38498-e38498
  • DOI: 10.1371/journal.pone.0038498
  • 査読あり
• [雑誌論文] Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson's disease : a 3-year longitudinal study (2012)
  • 著者名/発表者名: BabaT, Kikuchi A, Hirayama K, Nishio Y, Hosokai Y, Kanno S, Hasegawa T, Sugeno N, Konno M, Suzuki K, et al
  • 雑誌名: Brain 巻: 135 号: 1 ページ: 162-169
  • DOI: 10.1093/brain/awr321
  • 査読あり
• [学会発表] Hyposmia and cholinergic deficiency in Parkinson Disease (2014)
  • 著者名/発表者名: Takeda A.
  • 学会等名: The13th International Parkinson Disease Symposium in Takamatsu
  • 発表場所: Takamatsu, Japan
• [学会発表] In vivo visualization ofα-synuclein depositions in the human brain with multiple system atrophy and Parkinson's disease (2013)
  • 著者名/発表者名: Kikuchi A., Takeda A.
  • 学会等名: 1st Annual MJFF Alpha-Synuclein Imaging Summit
  • 発表場所: New York, USA
  • 年月日: 2013-11-08
• [学会発表] Search for rare-variant risks of Parkinson's disease by sequencing of candidate genes and exome sequencing (2013)
  • 著者名/発表者名: Satake W., Ando Y., Tomiyama H., Takeda A., Hasegawa K., Yamamoto M., Murata M., Hattori N., Toda T.
  • 学会等名: 17th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] RNAi-mediated silencing of VPS35 exacerbates phenotypic and locomotor abnormalities inα-synuclein transgenic drosophila (2013)
  • 著者名/発表者名: Hasegawa T., Konno M., Miura E., Sugeno N., Nagai Y., Fujikake N., Suzuki M., Kikuchi A., Aoki M., Takeda A.
  • 学会等名: 17th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] RNAi-mediated knockdown of VPS35 impairsα-synuclein degradation by inhibiting the maturation of cathepsin D (2013)
  • 著者名/発表者名: Miura E., Hasegawa T., Konno M., Sugeno N., Kikuchi A., Baba T., Aoki M., Takeda A.
  • 学会等名: 17th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] Nedd4 E3 ubiquitin ligase facilitates the endosomal targeting of alpha-synuclein (2013)
  • 著者名/発表者名: Sugeno N., Hasegawa T., Konno M., Miura E., Kikuchi A., Aoki M., Takeda A.
  • 学会等名: 17th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] Differentiating Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test (2013)
  • 著者名/発表者名: Kikuchi A., Baba T., Hasegawa T., Sugeno N., Konno M., Aoki M., Takeda A.
  • 学会等名: 17th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] Severe hyposmia is a prodromal symptom of dementia in Parkinson disease (2013)
  • 著者名/発表者名: Takeda A.
  • 学会等名: 9th International congress on mental dysfunction & other non-motor features in Parkinson's disease and related disorders
  • 発表場所: Seoul, South Korea
• [学会発表] Severe hyposmia is a prodromal symptom of dementia in Parkinson disease (2013)
  • 著者名/発表者名: Takeda A.
  • 学会等名: 9th International congress on mental dysfunction & other non-motor features in Parkinson’s disease and related disorders
  • 発表場所: Seoul, South Korea
  • 招待講演
• [学会発表] Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test (2013)
  • 著者名/発表者名: Kikuchi A. Baba T. Hasegawa T. Sugeno N. Konno M. Aoki M. Takeda A.
  • 学会等名: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] Nedd4 E3 ubiquitin ligase facilitates the endosomal targeting of alpha-synuclein (2013)
  • 著者名/発表者名: Sugeno N. Hasegawa T. Konno M. Miura E. Kikuchi A. Aoki M. Takeda A.
  • 学会等名: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] RNAi-mediated knockdown of VPS35 impairs α-synuclein degradation by inhibiting the maturation of cathepsin D (2013)
  • 著者名/発表者名: Miura E. Hasegawa T. Konno M. Sugeno N. Kikuchi A. Baba T. Aoki M. Takeda A.
  • 学会等名: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] RNAi-mediated silencing of VPS35 exacerbates phenotypic and locomotor abnormalities in α-synuclein transgenic drosophila (2013)
  • 著者名/発表者名: Hasegawa T. Konno M. Miura E. Sugeno N. Nagai Y. Fujikake N. Suzuki M. Kikuchi A. Aoki M. Takeda A.
  • 学会等名: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] Search for rare-variant risks of Parkinson's disease by sequencing of candidate genes and exome sequencing (2013)
  • 著者名/発表者名: Satake W. Ando Y. Tomiyama H. Takeda A. Hasegawa K. Yamamoto M. Murata M. Hattori N. Toda T.
  • 学会等名: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Sydney, Australia
• [学会発表] Japanese 2nd GWAS identifies strong association at a novel risk locus and MCCC1 for Parkinson's disease (2012)
  • 著者名/発表者名: Satake W., Yamamoto K., Ando Y., Takeda A., Tomiyama H., Kawakami H., Hasegawa K., Obata F., Watanabe M., Tamaoka A., Nakashima K., Sakoda S., Yamamoto M., Hattori N., Murata M., Nakamura Y., Toda T.
  • 学会等名: 16th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting ofα-synuclein (2012)
  • 著者名/発表者名: Hasegawa T., Konno M., Baba T., Sugeno N., Kikuchi A., Miura E., Takeda A.
  • 学会等名: 16th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Severe olfactory dysfunction is predictive of dementia associated with Parkinson's disease : A 3-year longitudinal study (2012)
  • 著者名/発表者名: Baba T., Kikuchi A., Hirayama K., Nishio Y., Hosokai Y., Kanno S., Hasegawa T., Sugeno N., Konno M., Miura E., Mori E., Takeda A.
  • 学会等名: 16th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Dynamin GTPase activity decreases alpha-synuclein uptake in neuronal and oligodendroglial cells (2012)
  • 著者名/発表者名: Konno M., Hasegawa T., Baba T., Miura E., Sugeno N., Kikuchi A., Aoki M., Takeda A.
  • 学会等名: 16th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] The E3 ligase Nedd4 participates in the internalization process of alpha-synuclein (2012)
  • 著者名/発表者名: Sugeno N., Hasegawa T., Konno M., Miura E., Baba T., Kikuchi A., Aoki M., Takeda A.
  • 学会等名: 16th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Neural basis of memory impairment in Parkinson's disease : A longitudinal PET study (2012)
  • 著者名/発表者名: Shoji Y., Nishio Y., Takeda A., Uchiyama M., Kashinoura T., Hosokai Y., Fukuda H., Mori E.
  • 学会等名: 16th International Congress of Parkinson's Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of α-synuclein (2012)
  • 著者名/発表者名: Hasegawa T., Konno M., Baba T., Sugeno N., Kikuchi A., Miura E., Takeda A.
  • 学会等名: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Severe olfactory dysfunction is predictive of dementia associated with Parkinson’s disease: A 3-year longitudinal study (2012)
  • 著者名/発表者名: Baba T., Kikuchi A., Hirayama K., Nishio Y., Hosokai Y., Kanno S., Hasegawa T., Sugeno N., Konno M., Miura E., Mori E., Takeda A.
  • 学会等名: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Dynamin GTPase activity decreases alpha-synuclein uptake in neuronal and oligodendroglial cells (2012)
  • 著者名/発表者名: Konno M., Hasegawa T., Baba T., Miura E., Sugeno N., Kikuchi A., Aoki M., Takeda A.
  • 学会等名: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Nedd4 participates in the internalization process of alpha-synuclein (2012)
  • 著者名/発表者名: Sugeno N., Hasegawa T., Konno M., Miura E., Baba T., Kikuchi A., Aoki M., Takeda A.
  • 学会等名: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Neural basis of memory impairment in Parkinson’s disease: A longitudinal PET study (2012)
  • 著者名/発表者名: Shoji Y., Nishio Y., Takeda A., Uchiyama M., Kashinoura T., Hosokai Y., Fukuda H., Mori E.
  • 学会等名: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [学会発表] Japanese 2nd GWAS identifies strong association at a novel risk locus and MCCC1 for Parkinson’s disease (2012)
  • 著者名/発表者名: Satake W., Yamamoto K., Ando Y., Takeda A., et al.
  • 学会等名: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • 発表場所: Dublin, Ireland
• [図書] パーキンソン病、「ガイドライン外来診療2013」(泉孝英編) (2013)
  • 著者名/発表者名: 武田篤
  • 出版者: 日経メディカル開発
• [図書] (第5章)パーキンソン病とその他の症状や疾患その考え方と対応パーキンソン病と嗅覚障害の関係は?【あなたも名医!ここを押さえる!パーキンソン病診療34のギモンに答える】jmed mook23号 (2012)
  • 著者名/発表者名: 馬場徹、武田篤
  • 出版者: 日本医事新報社
• [図書] パーキンソン病の病因・病態生理、「GP・レジデントのためのパーキンソン病テキストブック」(山本光利編) (2012)
  • 著者名/発表者名: 武田篤
  • 出版者: アルタ出版
• [図書] 痙性斜頚のPET、「ジストニア2012」(長谷川一子編) (2012)
  • 著者名/発表者名: 武田篤、菊池昭夫
  • 出版者: 中外医学社