Association between MicroRNA Dysregulation and Oxidative Damage in Brains with Alzheimer's Disease

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591698
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Yamanashi
• Principal Investigator: NUNOMURA Akihiko 山梨大学, 医学工学総合研究部, 准教授 (60241436)
• Project Period (FY): 2011 – 2013
• Keywords: 認知症 / アルツハイマー病 / 加齢脳 / 酸化ストレス / RNA / ミトコンドリアDNA / 認知機能障害 / アメリカ合衆国

Research Abstract

An in situ approach in the cerebral cortex of postmortem brains revealed that levels of oxidative damage to nucleic acids in neurons increased during aging and remarkably increased at the stage of very mild Alzheimer's disease. The neuronal nucleic acids oxidation in aging was significantly associated with mitochondrial DNA deletion, and both of them were regarded as crucial alterations in the prodromal stage of neurodegeneration.In this study, however, specific reactions of microRNA were hardly detected in postmortem brains, which suggested requirements of strictly controlled conditions in the processing of the brains to investigate microRNA in situ.

Research Products

• [Journal Article] 精神疾患の病態における酸化ストレスの役割 (2014)
  • Author(s): 布村明彦
  • Journal Title: 精神神経学雑誌 Volume: 116巻 (印刷中)
  • Peer Reviewed
• [Journal Article] Accumulation of Intraneuronal amyloid-βis common in normal brain (2014)
  • Author(s): Blair JA, Siedlak SL, Wolfram JA, Nunomura A, Castellani RJ, Ferreira ST, Klein WL, Wang Y, Casadesus G, Smith MA, Perry G, Zhu X, Lee HG
  • Journal Title: Current Alzheimer Research Volume: 11巻 Pages: 317-324
  • DOI: 10.2174/1567205011666140302200902
  • Peer Reviewed
• [Journal Article] 酸化ストレス仮説に基づくアルツハイマー病治療法開発の現状と展望 (2013)
  • Author(s): 布村明彦
  • Journal Title: 臨床神経学 Volume: 53巻 Pages: 1043-1045
  • DOI: 10.5692/clinicalneurol.53.1043
• [Journal Article] Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links (2013)
  • Author(s): Perry EA, Castellani RJ, Moreira PI, Nunomura A, Lui Q, Harris PL, Sayre LM, Szweda PA, Szweda LI, Zhu X, Smith MA, Perry G
  • Journal Title: Free Radical Research Volume: 47巻 Pages: 507-510
  • DOI: 10.3109/10715762.2013
  • Peer Reviewed
• [Journal Article] Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease (2013)
  • Author(s): Santos RX, Correia SC, Zhu X, Smith MA, Moreira PI, Castellani RJ, Nunomura A, Perry G
  • Journal Title: Antioxidants & Redox Signaling Volume: 18巻 Pages: 2444-2457
  • DOI: 10.1089/ars.2012.5039
  • Peer Reviewed
• [Journal Article] Preclinical ADとMCI脳を分ける変化:酸化障害 (2013)
  • Author(s): 布村明彦,玉置寿男
  • Journal Title: Dementia Japan Volume: 27巻 (J-GLOBAL ID:201302273914323518) Pages: 237-243
• [Journal Article] アルツハイマー病診断のバイオマーカー―最近の進歩―酸化ストレスマーカー (2013)
  • Author(s): 布村明彦,玉置寿男
  • Journal Title: 老年精神医学雑誌 Volume: 24巻 (J-GLOBAL ID:201302224251908346) Pages: 140-147
• [Journal Article] 加齢と神経変性疾患におけるRNA酸化傷害 (2013)
  • Author(s): 布村明彦
  • Journal Title: Brain and Nerve Volume: 65巻 (J-GLOBAL ID:201302235672002097) Pages: 179-194
• [Journal Article] The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons (2012)
  • Author(s): Nunomura A, Tamaoki T, Motohashi N, Nakamura M, McKeel DW Jr, Tabaton M, Lee HG, Smith MA, Perry G, Zhu X
  • Journal Title: Journal of Neuropathology and Experimental Neurology Volume: 71巻 Pages: 233-241
  • DOI: 10.1097/NEN.0b013e318248e614
  • Peer Reviewed
• [Journal Article] Oxidative damage to RNA in aging and neurodegenerative disorders (2012)
  • Author(s): Nunomura A, Moreira PI, Castellani RJ, Lee HG, Zhu X, Smith MA, Perry G
  • Journal Title: Neurotoxicity Research Volume: 22巻 Pages: 231-248
  • DOI: 10.1007/s12640-012-9331-x
  • Peer Reviewed
• [Journal Article] Nuclear and mitochondrial DNA oxidation in Alzheimer's disease (2012)
  • Author(s): Santos RX, Correia SS, Zhu X, Lee HG, Petersen RB, Nunomura A, Perry G, Smith MA, Moreira PI
  • Journal Title: Free Radical Research Volume: 46巻 Pages: 565-576
  • DOI: 10.3109/10715762.2011.648188
  • Peer Reviewed
• [Journal Article] A novel perspective on tau in Alzheimer disease (2012)
  • Author(s): Bonda DJ, Castellani RJ, Zhu X, Nunomura A, Lee HG, Perry G, Smith MA
  • Journal Title: Current Alzheimer Research Volume: 8(6) Pages: 639-642
  • DOI: 10.2174/156720511796717131
  • Peer Reviewed
• [Journal Article] 認知症学(下)―その解明と治療の最新知見―Vascular cognitive impairment (2011)
  • Author(s): 布村明彦,玉置寿男
  • Journal Title: 日本臨床 Volume: 69巻増刊号10 (J-GLOBAL ID:201102268280459472) Pages: 325-330
• [Journal Article] アルツハイマー病根本治療薬の開発 (2011)
  • Author(s): 布村明彦
  • Journal Title: 精神科 Volume: 19巻 (J-GLOBAL ID:201202284976361275) Pages: 502-508
• [Journal Article] アルツハイマー病:予防診療の進歩 (2011)
  • Author(s): 布村明彦
  • Journal Title: 最新医学 Volume: 66巻9月増刊号 (J-GLOBAL ID:201102210946622677) Pages: 2133-2145
• [Presentation] RNA酸化傷害と認知症疾患 (2014)
  • Author(s): 布村明彦
  • Organizer: 第33回日本認知症学会学術集会シンポジウム
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 20141129-1201
  • Invited
• [Presentation] 精神疾患の病態における酸化ストレスの役割 (2014)
  • Author(s): 布村明彦
  • Organizer: 第110回日本精神神経学会学術総会シンポジウム
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 20140626-28
  • Invited
• [Presentation] ストレスと認知症 (2014)
  • Author(s): 布村明彦
  • Organizer: 第14回日本抗加齢医学会総会シンポジウム
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 20140606-08
  • Invited
• [Presentation] Oxidative RNA damage in diverse neuropsychiatric disorders (2013)
  • Author(s): Nunomura A
  • Organizer: 8th Brain Research Conference RNA Metabolism in Neurological Disease
  • Place of Presentation: Sheraton San Diego Hotel and Marina, San Diego, CA, USA
  • Year and Date: 20131107-08
• [Presentation] Oxidative damage to RNA in aging and neurodegenerative disorders (2013)
  • Author(s): Nunomura A
  • Organizer: 11th International Conference on Environment Mutagens
  • Place of Presentation: Bourbon Convention & Spa Resort Cataratas do Iguass, Foz do Iguass, PR, Brazil
  • Year and Date: 20131103-08
  • Invited
• [Presentation] Oxidative RNA damage and repair (2013)
  • Author(s): Nunomura A
  • Organizer: 5th Meeting in Fundamental Aspects of DNA Repair and Mutagenesis
  • Place of Presentation: University of Sao Paulo, Sao Paulo, SP, Brazil
  • Year and Date: 20131031-1102
  • Invited
• [Presentation] 酸化ストレス仮説に基づくアルツハイマー病治療法開発の現状と展望 (2013)
  • Author(s): 布村明彦
  • Organizer: 第54回日本神経学会企画シンポジウム(認知症領域)
  • Place of Presentation: 東京国際フォーラム(東京都、千代田区)
  • Year and Date: 20130529-0601
  • Invited
• [Presentation] 多様な精神神経疾患における酸化傷害:早期介入のターゲットとしての重要性 (2013)
  • Author(s): 布村明彦
  • Organizer: 第109回日本精神神経学会トピック・フォーラム10
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 20130523-25
  • Invited
• [Presentation] 酸化ストレスと精神神経疾患 (2013)
  • Author(s): 布村明彦
  • Organizer: 第109回日本精神神経学会シンポジウム10
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 20130523-25
  • Invited
• [Presentation] Preclinical AD脳とMCI脳を分ける変化:酸化傷害(Oxidative Damage) (2011)
  • Author(s): 布村明彦
  • Organizer: 第30回日本認知症学会
  • Place of Presentation: タワーホール船堀(東京都江戸川区)
  • Year and Date: 20111111-13
  • Invited
• [Presentation] 第30回日本認知症学会 (2011)
  • Author(s): 布村明彦
  • Organizer: 加齢、preclinical AD、およびMCI脳における神経細胞内RNAの酸化傷害
  • Place of Presentation: タワーホール船堀(東京都江戸川区)
  • Year and Date: 20111111-13
• [Presentation] Neuronal RNA oxidation in age-related neurodegenerative disorders (2011)
  • Author(s): Nunomura A
  • Organizer: 2nd Annual World Congress of NeuroTalk-2011
  • Place of Presentation: Dalian World EXPO Center, Dalian, China
  • Year and Date: 20110522-25
  • Invited
• [Book] 認知症の診断、精神医学的診察、In : 認知症ハンドブック (2013)
  • Author(s): 布村明彦 (中島健二,天野直二,下濱俊,冨本秀和,三村將(編))
  • Total Pages: 133-140
  • Publisher: 医学書院、東京
• [Book] Thinking outside the box in Alzheimer disease treatment、In : Development of Therapeutic Agents (2011)
  • Author(s): Castellani RJ, Marlatt MW, Nunomura A, Moreira PI, Lee HG, Casadesus G, Zhu X, Perry G, Smith MA (Gad SC (Ed))
  • Total Pages: 929-942
  • Publisher: John Wiley & Sons, Inc.、Hoboken, NJ
• [Book] Oxidative stress and balance in neurodegenerative diseases、In : Neurodegeneration : The Molecular Pathology of Dementia and Movement Disorders, 2nd Edition, International Society of Neuropathology (2011)
  • Author(s): Perry G, Mondragón-Rodríguez S, Nunomura A, Zhu X, Moreira P, Smith MA (Dickson DW, Weller RO (Eds))
  • Total Pages: 10-12
  • Publisher: Wiley-Blackwell、Hoboken, NJ
• [Book] 認知症とうつ病、In :精神科研修ノート (2011)
  • Author(s): 布村明彦 (笠井清登,村井俊哉,三村將,岡本泰昌,大島紀人(編))
  • Total Pages: 309-311
  • Publisher: 診断と治療社、東京
• [Book] 神経疾患の脳研究から見た精神疾患研究の難しさ、In :脳バンク精神疾患の謎を解くために (2011)
  • Author(s): 布村明彦 (加藤忠史(編))
  • Total Pages: 77-85
  • Publisher: 光文社新書、東京
• [Book] Oxidative stress in Alzheimer's disease : a critical appraisal of the causes and the consequences、In : Studies on Experimental Models : Oxidative Stress in Applied Basic Research and Clinical Practice, Part 3 (2011)
  • Author(s): Chang J, Siedlak S, Moreira P, Nunomura A, Castellani RJ, Smith MA, Zhu X, Perry G, Casadesus G (Basu S, Wiklund L (Eds))
  • Total Pages: 211-220
  • Publisher: Springer Science+Business Media LLC、New York
• [Remarks] ホームページ
  • URL: http://erdb.yamanashi.ac.jp/rdb/A_DispInfo.Scholar?ID=7A340E6805978836