micro RNA as a novel biomarker for neurodegenerative diseses

2013 Fiscal Year Final Research Report

• 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
• Keywords: パーキンソン病 / バイオマーカー / シヌクレイノパチー

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: Neurology and Clinical Neuroscience Volume: 1 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): Kikuchi A., Baba T., Hasegawa T., Kobayashi M., Sugeno N., Konno M., Miura E., Hosokai Y., Ishioka T., Nishio Y., Hirayama K., Suzuki K., Aoki M., Takahashi S., Fukuda H., Itoyama Y., Mori E., Takeda A.
  • Journal Title: BMJ Open Volume: 3 Pages: 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 Pages: 315-317
  • DOI: 10.1007/s00415-012-6730-0
  • Peer Reviewed
• [Journal Article] Suppression of dynamin GTPase decreasesα-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: Molecular Neurodegeneration Volume: 7 Pages: 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., Yanai K., Iwata R., Mori E.
  • Journal Title: Eur Neurol Volume: 68 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): Sawada Y., Nishio Y., Suzuki K., Hirayama K., Takeda A., Hosokai Y., Ishioka T., Itoyama Y., Takahashi S., Fukuda H., Mori E.
  • Journal Title: PLoS ONE Volume: 7 Pages: 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): Baba T., Kikuchi A., Hirayama K., Nishio Y., Hosokai Y., Kanno S., Hasegawa T., Sugeno N., Konno M., Suzuki K., Takahashi S., Fukuda H., Aoki M., Itoyama Y., Mori E., Takeda A.
  • Journal Title: Brain Volume: 135 Pages: 161-169
  • 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
  • Year and Date: 20140221-22
• [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
  • Year and Date: 20130616-20
• [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
  • Year and Date: 20130616-20
• [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
  • Year and Date: 20130616-20
• [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
  • Year and Date: 20130616-20
• [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
  • Year and Date: 20130616-20
• [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
  • Year and Date: 20130418-21
• [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] 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
  • Year and Date: 20120617-22
• [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
  • Year and Date: 20120617-22
• [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
  • Year and Date: 20120617-22
• [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
  • Year and Date: 20120617-22
• [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
  • Year and Date: 20120617-22
• [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
  • Year and Date: 20120617-22
• [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
  • Total Pages: 527-529
  • 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
  • Total Pages: 150-152
  • 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
  • Total Pages: 30-39
  • 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
  • Total Pages: 231-233
  • Publisher: 中外医学社