seeking the role of granulovacuolar degeneration in neurodegeneration

• Project/Area Number: 26461304
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Gunma University
• Principal Investigator: Yamazaki Tsuneo 群馬大学, 大学院保健学研究科, 教授 (80200658)
• Co-Investigator(Kenkyū-buntansha): 牧岡 幸樹 群馬大学, 医学部附属病院, 助教 (10420176)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 顆粒空胞変性 / オートファジー / タウ / 神経原線維変化 / シアル化 / 神経変性疾患 / オートファジー・ライソゾーム / ユビキチン-プロテアソーム

Outline of Final Research Achievements

The aim of this study is to seek the roles of abnormal protein degradation in neurodegeneration, especially Alzheimer disease. In results, we found that ubiquitin E3 ligases, Smurf1 and Tom1 are over-expressed in the disease related structures, Hirano body, dystrophic neurites and neurofibrillary tangles. We also found that over sialic acid reaction in granulovacuolar degeneration, dystrophic neurites and neurofibrillary tangles, and this reaction is strongly related to hyper-phosphorylated tau accumulation.

Research Products

• [Journal Article] Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains. (2016)
  • Author(s): Nagamine S, Yamazaki T, Makioka K, Fujita Y, Ikeda M, Takatama M, Okamoto K, Yokoo H, Ikeda Y.
  • Journal Title: Neuropathology Volume: 36 Issue: 4 Pages: 333-345
  • DOI: 10.1111/neup.12277
  • Peer Reviewed
• [Journal Article] Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease. (2016)
  • Author(s): Makioka K, Yamazaki T, Takatama M, Ikeda M, Murayama S, Okamoto K, Ikeda Y.
  • Journal Title: J Neurol Sci Volume: 365 Pages: 101-107
  • DOI: 10.1016/j.jns.2016.03.035
  • Peer Reviewed
• [Journal Article] Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains (2016)
  • Author(s): Nagamine S, Yamazaki T, Makioka K, Fujita Y, Ikeda M, Takatama M, Okamoto K, Yokoo H, Ikeda Y
  • Journal Title: Neuropathology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease (2016)
  • Author(s): Makioka K, Yamazaki T, Takatama M, Ikeda M, Murayama S, Okamoto K, Ikeda Y
  • Journal Title: Journal of Neurological Sciences Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunolocalization of Smurf1 in Hirano bodies. (2014)
  • Author(s): Makioka K, Yamazaki T, Takatama M, Ikeda M, Okamoto K
  • Journal Title: J Neurol Sci Volume: 336 Issue: 1-2 Pages: 24-28
  • DOI: 10.1016/j.jns.2013.09.028
  • Peer Reviewed / Open Access
• [Journal Article] SF levels of Aβ1-38/Aβ1-40/Aβ1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease. (2014)
  • Author(s): Ikeda M, Tashiro Y, Takai E, Kurose S, Fugami N, Tsuda K, Arisaka Y, KodairaS, Fujita Y, Makioka K, Mizuno Y, Shimada H, Harigaya Y, Takatama M, Amari M, Yamazaki T,Yamaguchi H, Higuchi T, Okamoto K, Tsushima Y, Ikeda Y.
  • Journal Title: Amyloid Volume: 21 Issue: 4 Pages: 238-245
  • DOI: 10.3109/13506129.2014.949231
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Repeated encephalopathy and hemicerebral atrophy in a patient with familial hemiplegic migraine type 1 (2014)
  • Author(s): Tashiro Y, Yamazaki T, Nagamine S, Mizuno Y, Yoshiki A, Okamoto K
  • Journal Title: Internal Medicine Volume: 53 Pages: 2245-2250
  • NAID: 130004694525
  • Peer Reviewed
• [Presentation] Immunolocalization of Tom1 and Tom1-Relating Proteins in Alzheimer’s disease (2015)
  • Author(s): Kouki Makioka, Tsuneo Yamazaki, Masamitsu Takatama, Koichi Okamoto, Yoshio Ikeda
  • Organizer: VAS-COG World 2015
  • Place of Presentation: Tokyo
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] Immunolocalization of Tom1 and Tom1-Relating Proteins in Alzheimer’s disease (2015)
  • Author(s): Kouki Makioka, Tsuneo Yamazaki, Masamitsu Takatama, Koichi Okamoto, Yoshio Ikeda
  • Organizer: Alzheimer’s Association International Conference 2015
  • Place of Presentation: Washington D.C
  • Year and Date: 2015-07-18
  • Int'l Joint Research
• [Presentation] Alzheimer病におけるTom1の発現に関する免疫組織学的検討 (2014)
  • Author(s): 牧岡幸樹、山崎恒夫、高玉真光、岡本幸市、池田佳生
  • Organizer: 第33回日本認知症学会学術集会
  • Place of Presentation: パシフィコ横浜 会議センター（神奈川県横浜市）
  • Year and Date: 2014-12-01
• [Presentation] Hirano小体におけるSmurf1の発現について (2014)
  • Author(s): 牧岡幸樹、山崎恒夫、高玉真光、岡本幸市、池田佳生
  • Organizer: 第5回日本血管性認知障害研究会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2014-08-23
• [Presentation] Immunolocalization of Tom1 in Alzheimer’s disease (2014)
  • Author(s): Kouki Makioka, Tsuneo Yamazaki, Masamitsu Takatama, Koichi Okamoto, Yoshio Ikeda
  • Organizer: Alzheimer’s Association International Conference 2014
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-07-20
• [Presentation] Alzheimer病におけるTOM1の発現に関する免疫組織学的検討 (2014)
  • Author(s): 牧岡幸樹、山崎恒夫、高玉真光、岡本幸市、池田佳生
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際センター（福岡県福岡市）
  • Year and Date: 2014-05-22