Demonstration of the abnormal conformational transition of amyloid proteins and it's application as an early diagnostic tool

2012 Fiscal Year Final Research Report

• Project/Area Number: 21200072
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry; Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: POPIEL HELENA Akiko 独立行政法人国立精神・神経医療研究センター, 神経研究所・疾病研究第四部, 科研費研究員 (40467593)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Yoshitaka 独立行政法人国立精神・神経医療研究センター, 神経研究所・疾病研究第四部, 室長 (60335354) ; AOKI Masashi 東北大学, 医学系研究科・神経内科学分野, 教授 (70302148)
• Project Period (FY): 2009 – 2012
• Keywords: 神経変性疾患 / ポルグルタミン病 / バイオマーカー / コンフォメーション伝播 / アミロイド

Research Abstract

In the prion diseases, the abnormal structure of the disease-causing protein is transmitted to proteins with a normal structure. In this study, we aimed to elucidate whether the abnormal structure of the disease-causing proteins of the polyglutamine (polyQ) neurodegenerative diseases can also be transmitted, and whether this phenomenon could be used for detection of minute levels of abnormal polyQ proteins. We found that addition of a minute level of abnormal polyQ protein to normal polyQ proteins causes acceleration of the structural transition of the proteins. Furthermore, for detection of proteins with an abnormal structure, we analyzed systems involving both turbidity as well as fluorescence, and found that they both had equal sensitivity. We also determined a purification method of the polyQ protein that allows structural transition of the protein at high efficiency.

Research Products

• [Journal Article] Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine diseases (2013)
  • Author(s): Popiel HA, Takeuchi T, Burke JR, Strittmatter WJ, Toda T, Wada K, Nagai Y
  • Journal Title: Neurotherapeutics Volume: (in press)
  • URL: http://link.springer.com/article/10.1007%2Fs13311-013-0184-7
  • Peer Reviewed
• [Journal Article] Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism (2013)
  • Author(s): Popiel HA, Takeuchi T, Fujita H, Yamamoto K, Ito C, Yamane H, Muramatsu S, Toda T, Wada K, Nagai Y
  • Journal Title: PLoS ONE Volume: 7(11) Pages: e52069
  • DOI: DOI: 10.1371/journal.pone.0051069
  • Peer Reviewed
• [Journal Article] The aggregation inhibitor peptide QBP1 as a therapeutic molecule for the polyglutamine neurodegenerative diseases (2011)
  • Author(s): Popiel HA, Burke JR, Strittmatter WJ, Oishi S, Fujii N, Takeuchi T, Toda T, Wada K, Nagai Y
  • Journal Title: J Amino Acids Volume: 2011 Pages: 265084
  • DOI: DOI: 10.4061/2011/265084
  • Peer Reviewed
• [Journal Article] Genetic testing for Huntington's disease in Parkinsonism (2010)
  • Author(s): Rahman MS, Nagai Y, Popiel HA, Fujikake N, Okamoto Y, Ahmed MU, Islam MA, Islam MT, Ahmed S, Rahman KM, Uddin MJ, Dey SK, Ahmed Q, Hossain MA, Jahan N, Toda T
  • Journal Title: Mymensingh Med J Volume: 19 Pages: 510-514
  • URL: http://www.banglajol.info/index.php/MMJ/article/view/6708
  • Peer Reviewed
• [Journal Article] Induction of molecular chaperones as a therapeutic strategy for the polyglutamine diseases (2010)
  • Author(s): Nagai Y, Fujikake N, Popiel HA, Wada K
  • Journal Title: Curr Pharm Biotechnol Volume: 11 Pages: 188-197
  • URL: http://www.eurekaselect.com/71304/article
  • Peer Reviewed
• [Presentation] 凝集阻害分子の遺伝子治療によるポリグルタミン病モデルマウスに対する治療効果 (2011)
  • Author(s): ポピエル ヘレナ 明子
  • Organizer: 第52回に本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] Molecular chaperone gene therapy ameliorates neurological phenotypes and protein aggregation in polyglutamine neurodegenerative disease mice (2010)
  • Author(s): Popiel HA
  • Organizer: 3^<rd> International Symposium on Protein Community
  • Place of Presentation: 奈良
  • Year and Date: 2010-09-13
• [Presentation] 凝集阻害分子を用いた遺伝子治療によるポリグルタミン病モデルマウスの神経症状と封入体形成の抑制 (2010)
  • Author(s): ポピエル 明子
  • Organizer: 第33回日本神経科学会・第53回日本神経科学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] ポリグルタミン病モデルマウスに対する凝集阻害ペプチドQBP1 を用いた遺伝子治療 (2009)
  • Author(s): ポピエル 明子
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] Towards designing chemical analogues of the polyglutamine aggregation inhibitor peptide QBP1: a structure-activity relationship study on QBP1 (2009)
  • Author(s): Popiel HA
  • Organizer: 5^<th> Gordon Research Conference on CAG Triplet Repeat Disorders
  • Place of Presentation: New Hampshire, USA
  • Year and Date: 2009-05-31
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r4/index.html