micro RNA as a novel biomarker for neurodegenerative diseses

• Project/Area Number: 24659423
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: TAKEDA Atsushi 東北大学, 医学(系)研究科(研究院), 非常勤講師 (70261534)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 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

Research Abstract

We analyzed miRNAs in exosome fractions of human cerebrospinal fluid (CSF). The CSF was collected from five cases with Parkinson disease (PD) and three control cases. The samples were analyzed by using the miRBase ver19.0 (Agilent) and several miRNAs were identified to be significantly increased or decreased. By using the three algorithms, TargetScan, miRDB and DIANA LAB, gene X was revealed to be a target gene of the miR-1xxx. The protein product of gene X is known to play a key role in the post-translational modification of alpha-synuclein, suggesting the changes of miRNA levels in CSF are reflecting pathophyisiological processes in PD brain.

Research Products

• [Journal Article] Cognitive impairment in multiple system atrophy : A position statement by the Neuropsychology Task Force of the MDS multiple system atrophy (MODIMSA) Study Group (2014)
  • Author(s): 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.
  • Journal Title: Movement Disorders Volume: (in press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24753321
  • Peer Reviewed
• [Journal Article] Olfactory dysfunction and dementia in Parkinson's disease (2014)
  • Author(s): Takeda A., Baba T., Kikuchi A., Hasegawa T., Sugeno N., Konno M., Miura E., Mori E.
  • Journal Title: J. Parkinsons Dis Volume: (in press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24625830
  • Peer Reviewed
• [Journal Article] Pathogenesis of Multiple system atrophy. (2013)
  • Author(s): Hasegawa T, Kikuchi A, Takeda A.
  • Journal Title: Neurol Clin Neurosci Volume: 1 (6) Issue: 6 Pages: 189-194
  • DOI: 10.1111/ncn3.57
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): 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
  • Journal Title: BMJ Open Volume: 3 Issue: 3 Pages: e002249-e002249
  • DOI: 10.1136/bmjopen-2012-002249
  • Peer Reviewed
• [Journal Article] Anti-voltage-gated potassium channel antibody is associated with chronic autonomic and sensory neuropathy. (2013)
  • Author(s): Kaneko K, Tano O, Kikuchi A, Hasegawa T, Tateyama M, Yoshioka M, Saito H, Watanabe O, Takeda A, Aoki M.
  • Journal Title: J Neurol Volume: 260 Issue: 1 Pages: 315-317
  • DOI: 10.1007/s00415-012-6730-0
  • Peer Reviewed
• [Journal Article] Suppression of dynamin GTPase decreases alpha-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy. (2012)
  • Author(s): Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, Kikuchi A, Fiesel FC, Sasaki T, Aoki M, Itoyama Y, Takeda A.
  • Journal Title: Mol Neurodegener Volume: 7 Issue: 1 Pages: 38-38
  • DOI: 10.1186/1750-1326-7-38
  • Peer Reviewed
• [Journal Article] Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia (2012)
  • Author(s): Hiraoka K, Okamura N, Funaki Y, Hayashi A, Tashiro M, Hisanaga K, Fujii T, Takeda A, Y anai K, Iwata R, Mori E
  • Journal Title: Eur Neurol Volume: 68 Issue: 3 Pages: 137-143
  • DOI: 10.1159/000338774
  • Peer Reviewed
• [Journal Article] Attentional Set-Shifting Deficit in Parkinson's Disease Is Associated with Prefrontal Dysfunction: An FDG-PET Study (2012)
  • Author(s): Yoichi Sawada, Yoshiyuki Nishio, Kyoko Suzuki, Kazumi Hirayama, Atsushi Takeda, Yoshiyuki Hosokai, Toshiyuki Ishioka, Yasuto Itoyama, Shoki Takahashi, Hiroshi Fukuda, Etsuro Mori
  • Journal Title: PLoS ONE Volume: 7(6) Issue: 6 Pages: e38498-e38498
  • DOI: 10.1371/journal.pone.0038498
  • Peer Reviewed
• [Journal Article] Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson's disease : a 3-year longitudinal study (2012)
  • Author(s): BabaT, Kikuchi A, Hirayama K, Nishio Y, Hosokai Y, Kanno S, Hasegawa T, Sugeno N, Konno M, Suzuki K, et al
  • Journal Title: Brain Volume: 135 Issue: 1 Pages: 162-169
  • DOI: 10.1093/brain/awr321
  • Peer Reviewed
• [Presentation] Hyposmia and cholinergic deficiency in Parkinson Disease (2014)
  • Author(s): Takeda A.
  • Organizer: The13th International Parkinson Disease Symposium in Takamatsu
  • Place of Presentation: Takamatsu, Japan
• [Presentation] In vivo visualization ofα-synuclein depositions in the human brain with multiple system atrophy and Parkinson's disease (2013)
  • Author(s): Kikuchi A., Takeda A.
  • Organizer: 1st Annual MJFF Alpha-Synuclein Imaging Summit
  • Place of Presentation: New York, USA
  • Year and Date: 2013-11-08
• [Presentation] Search for rare-variant risks of Parkinson's disease by sequencing of candidate genes and exome sequencing (2013)
  • Author(s): Satake W., Ando Y., Tomiyama H., Takeda A., Hasegawa K., Yamamoto M., Murata M., Hattori N., Toda T.
  • Organizer: 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] RNAi-mediated silencing of VPS35 exacerbates phenotypic and locomotor abnormalities inα-synuclein transgenic drosophila (2013)
  • Author(s): Hasegawa T., Konno M., Miura E., Sugeno N., Nagai Y., Fujikake N., Suzuki M., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] RNAi-mediated knockdown of VPS35 impairsα-synuclein degradation by inhibiting the maturation of cathepsin D (2013)
  • Author(s): Miura E., Hasegawa T., Konno M., Sugeno N., Kikuchi A., Baba T., Aoki M., Takeda A.
  • Organizer: 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Nedd4 E3 ubiquitin ligase facilitates the endosomal targeting of alpha-synuclein (2013)
  • Author(s): Sugeno N., Hasegawa T., Konno M., Miura E., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Differentiating Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test (2013)
  • Author(s): Kikuchi A., Baba T., Hasegawa T., Sugeno N., Konno M., Aoki M., Takeda A.
  • Organizer: 17th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Severe hyposmia is a prodromal symptom of dementia in Parkinson disease (2013)
  • Author(s): Takeda A.
  • Organizer: 9th International congress on mental dysfunction & other non-motor features in Parkinson's disease and related disorders
  • Place of Presentation: Seoul, South Korea
• [Presentation] Severe hyposmia is a prodromal symptom of dementia in Parkinson disease (2013)
  • Author(s): Takeda A.
  • Organizer: 9th International congress on mental dysfunction & other non-motor features in Parkinson’s disease and related disorders
  • Place of Presentation: Seoul, South Korea
  • Invited
• [Presentation] Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test (2013)
  • Author(s): Kikuchi A. Baba T. Hasegawa T. Sugeno N. Konno M. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Nedd4 E3 ubiquitin ligase facilitates the endosomal targeting of alpha-synuclein (2013)
  • Author(s): Sugeno N. Hasegawa T. Konno M. Miura E. Kikuchi A. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] RNAi-mediated knockdown of VPS35 impairs α-synuclein degradation by inhibiting the maturation of cathepsin D (2013)
  • Author(s): Miura E. Hasegawa T. Konno M. Sugeno N. Kikuchi A. Baba T. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] RNAi-mediated silencing of VPS35 exacerbates phenotypic and locomotor abnormalities in α-synuclein transgenic drosophila (2013)
  • Author(s): Hasegawa T. Konno M. Miura E. Sugeno N. Nagai Y. Fujikake N. Suzuki M. Kikuchi A. Aoki M. Takeda A.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Search for rare-variant risks of Parkinson's disease by sequencing of candidate genes and exome sequencing (2013)
  • Author(s): Satake W. Ando Y. Tomiyama H. Takeda A. Hasegawa K. Yamamoto M. Murata M. Hattori N. Toda T.
  • Organizer: 17th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Sydney, Australia
• [Presentation] Japanese 2nd GWAS identifies strong association at a novel risk locus and MCCC1 for Parkinson's disease (2012)
  • Author(s): 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.
  • Organizer: 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting ofα-synuclein (2012)
  • Author(s): Hasegawa T., Konno M., Baba T., Sugeno N., Kikuchi A., Miura E., Takeda A.
  • Organizer: 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Severe olfactory dysfunction is predictive of dementia associated with Parkinson's disease : A 3-year longitudinal study (2012)
  • Author(s): Baba T., Kikuchi A., Hirayama K., Nishio Y., Hosokai Y., Kanno S., Hasegawa T., Sugeno N., Konno M., Miura E., Mori E., Takeda A.
  • Organizer: 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Dynamin GTPase activity decreases alpha-synuclein uptake in neuronal and oligodendroglial cells (2012)
  • Author(s): Konno M., Hasegawa T., Baba T., Miura E., Sugeno N., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] The E3 ligase Nedd4 participates in the internalization process of alpha-synuclein (2012)
  • Author(s): Sugeno N., Hasegawa T., Konno M., Miura E., Baba T., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Neural basis of memory impairment in Parkinson's disease : A longitudinal PET study (2012)
  • Author(s): Shoji Y., Nishio Y., Takeda A., Uchiyama M., Kashinoura T., Hosokai Y., Fukuda H., Mori E.
  • Organizer: 16th International Congress of Parkinson's Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of α-synuclein (2012)
  • Author(s): Hasegawa T., Konno M., Baba T., Sugeno N., Kikuchi A., Miura E., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Severe olfactory dysfunction is predictive of dementia associated with Parkinson’s disease: A 3-year longitudinal study (2012)
  • Author(s): Baba T., Kikuchi A., Hirayama K., Nishio Y., Hosokai Y., Kanno S., Hasegawa T., Sugeno N., Konno M., Miura E., Mori E., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Dynamin GTPase activity decreases alpha-synuclein uptake in neuronal and oligodendroglial cells (2012)
  • Author(s): Konno M., Hasegawa T., Baba T., Miura E., Sugeno N., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Nedd4 participates in the internalization process of alpha-synuclein (2012)
  • Author(s): Sugeno N., Hasegawa T., Konno M., Miura E., Baba T., Kikuchi A., Aoki M., Takeda A.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Neural basis of memory impairment in Parkinson’s disease: A longitudinal PET study (2012)
  • Author(s): Shoji Y., Nishio Y., Takeda A., Uchiyama M., Kashinoura T., Hosokai Y., Fukuda H., Mori E.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Presentation] Japanese 2nd GWAS identifies strong association at a novel risk locus and MCCC1 for Parkinson’s disease (2012)
  • Author(s): Satake W., Yamamoto K., Ando Y., Takeda A., et al.
  • Organizer: 16th International Congress of Parkinson’s Disease and Movement Disorders
  • Place of Presentation: Dublin, Ireland
• [Book] パーキンソン病、「ガイドライン外来診療2013」(泉孝英編) (2013)
  • Author(s): 武田篤
  • Publisher: 日経メディカル開発
• [Book] (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)
  • Author(s): 馬場徹、武田篤
  • Publisher: 日本医事新報社
• [Book] 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)
  • Author(s): 武田篤
  • Publisher: アルタ出版
• [Book] 痙性斜頚のPET、「ジストニア2012」(長谷川一子編) (2012)
  • Author(s): 武田篤、菊池昭夫
  • Publisher: 中外医学社