Research on the role of Omi/HtrA2 in the abnormal mitochondria in patients with Parkinson's disease

• Project/Area Number: 22590930
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto University
• Principal Investigator: KAWAMOTO Yasuhiro 京都大学, 医学研究科, 非常勤講師 (40335253)
• Co-Investigator(Kenkyū-buntansha): ITO Hidefumi 京都大学, 医学研究科, 講師 (20250061) ; TAKAHASHI Ryosuke 京都大学, 医学研究科, 教授 (90216771)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: Omi/HtrA2 / パーキンソン病 / ミトコンドリア / アポトーシス / XIAP / α-synuclein / parkin

Research Abstract

We confirmed that Lewy bodies were immunoreactive for XIAP, which is negatively regulated by Omi/HtrA2, and that XIAP and Omi/HtrA2 immunoreactivity were co-localized to Lewy bodies. Our research focused on apoptosome-related proteins demonstrated the immunohistochemical localization of cytochrome c, Apaf-1 and caspase-9 in Lewy bodies. We also found that cleaved caspase-9 immunoreactivity was localized to Lewy bodies, suggesting that caspase-9 may be activated in brains from patients with Parkinson’s disease.

Research Products

• [Journal Article] XIAP immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy (2013)
  • Author(s): Y. Kawamoto
  • Journal Title: Clinical Neuropathology (in press) Volume: undecicided
  • Peer Reviewed
• [Journal Article] Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies (2012)
  • Author(s): Kawamoto Y, Ito H, Ihara M, Takahashi R
  • Journal Title: NeuroReport Volume: 23:162-167 Issue: 3 Pages: 162-167
  • DOI: 10.1097/wnr.0b013e32834f4066
  • NAID: 120005244628
  • Peer Reviewed
• [Journal Article] Motor neuron-specific disruption of proteasomes, but not autophagy, replicates amyotrophic lateral sclerosis (2012)
  • Author(s): Y. Tashiro
  • Journal Title: Journal of Biological Chemistry Volume: 287 Issue: 51 Pages: 42984-42994
  • DOI: 10.1074/jbc.m112.417600
  • Peer Reviewed
• [Journal Article] An autopsy case of SOD1-related ALS with TDP-43 positive inclusions (2011)
  • Author(s): Okamoto Y, Ihara M, Urushitani M, Yamashita H, Kondo T, Tanigaki A, Oono M, Kawamata J, Ikemoto A, Kawamoto Y, Takahashi R, Ito H
  • Journal Title: Neurology Volume: 77:1993-1995 Issue: 22 Pages: 1993-1995
  • DOI: 10.1212/wnl.0b013e31823a0cfc
  • Peer Reviewed
• [Journal Article] Co localization of 14-3-3 proteins with SOD1 in Lewy Body-like hyaline inclusions in familial amyotrophic lateral sclerosis cases and the animal model (2011)
  • Author(s): Okamoto Y, Shirakashi Y, Ihara M, Urushitani M, Oono M, Kawamoto Y, Yamashita H, Shimohama S, Kato S, Hirano A, Tomimoto H, Ito H, Takahashi R
  • Journal Title: PLoS One Volume: 6 Issue: 5 Pages: e20427-e20427
  • DOI: 10.1371/journal.pone.0020427
  • Peer Reviewed
• [Journal Article] Clinicopathologic study on an ALS family with a heterozygous E478G optineurin mutation (2011)
  • Author(s): Ito H, Nakamura M, Komure O, Ayaki T, Wate R, Maruyama H, Nakamura Y, FujitaK, Kaneko S, Okamoto Y, Ihara M, Konishi T, Ogasawara K, Hirano A, Kusaka H, KajiR, Takahashi R, Kawakami H
  • Journal Title: Acta Neuropathologica Volume: 122 Issue: 2 Pages: 223-229
  • DOI: 10.1007/s00401-011-0842-y
  • Peer Reviewed
• [Journal Article] Optineurin is co-localized with FUS in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease (2011)
  • Author(s): Ito H, Fujita K, Nakamura M, Wate R, Kaneko S, Sasaki S, Yamane K, Suzuki N, Aoki M, Shibata N, Togashi S, Kawata A, Mochizuki Y, Mizutani T, Maruyama H, Hirano A, Takahashi R, Kawakami H, Kusaka H
  • Journal Title: Acta Neuropathologica Volume: 121 Issue: 4 Pages: 555-557
  • DOI: 10.1007/s00401-011-0809-z
  • Peer Reviewed
• [Journal Article] Localization of HtrA2/Omi immunoreactivity in brains with Alzheimer's disease (2010)
  • Author(s): Kawamoto Y, Ito H, Ihara M, Kobayashi Y, Suzuki Y, Takahashi R
  • Journal Title: Neuroreport Volume: 21 Issue: 17 Pages: 1121-1125
  • DOI: 10.1097/wnr.0b013e328340a731
  • Peer Reviewed
• [Journal Article] HtrA2/Omi-immunoreactive intraneuronal inclusions in the anterior horn of patients with sporadic and SOD1 mutant amyotrophic lateral sclerosis (2010)
  • Author(s): Kawamoto Y, Ito H, Kobayashi Y, Suzuki Y, Akiguchi I, Fujimura H, Sakoda S, Kusaka H, Hirano A, Takahashi R
  • Journal Title: Neuropathology and Applied Neurobiology Volume: 36 Issue: 4 Pages: 331-344
  • DOI: 10.1111/j.1365-2990.2010.01075.x
  • Peer Reviewed
• [Journal Article] HtrA2/Omi immunoreactive neuronal inclusions in the anterior horn of patients with sporadic and Cu/Zn superoxide dismutase(SOD1)mutant amyotrophic lateral sclerosis (2010)
  • Author(s): Y.Kawamoto, et al.
  • Journal Title: Neuropathology and Applied Neurobiology Volume: 36 Pages: 331-344
  • Peer Reviewed
• [Journal Article] Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer's disease (2010)
  • Author(s): Y.Kawamoto, et al.
  • Journal Title: NeuroReport Volume: 21 Pages: 1121-1125
  • Peer Reviewed
• [Journal Article] XIAP immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy
  • Author(s): Kawamoto Y, Ito H, Ihara M, Takahashi R
  • Journal Title: Clinical Neuropathology Volume: (in press)
  • Peer Reviewed
• [Presentation] パーキンソン病患者の中脳黒質のLewy小体におけるapoptosome関連タンパク質の集積 (2013)
  • Author(s): 河本恭裕
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-01
• [Presentation] 多系統萎縮症患者脳内の封入体におけるXIAPの蓄積 (2012)
  • Author(s): 河本恭裕
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-25
• [Presentation] Alzheimer病患者脳内におけるHtrA2/Omiの免疫組織化学的検討 (2011)
  • Author(s): 河本恭裕
  • Organizer: 第52回日本神経病理学会総会学術研究会
  • Place of Presentation: 京都
  • Year and Date: 2011-06-04
• [Presentation] 脳幹型および皮質型Lewy小体におけるXIAPとHtrA2/Omiの共存 (2011)
  • Author(s): 河本恭裕
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] Alzheimer病患者脳内におけるHtrA2/Omiの免疫組織化学的検討 (2010)
  • Author(s): 河本恭裕
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] Alzheimer病患者脳内におけるOmi/HtrA2の免疫組織化学的検討 (2010)
  • Author(s): 河本恭裕
  • Organizer: 第51会日本神経学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2010-05-22
• [Presentation] 多系統委縮症患者脳内の封入体におけるXIAPの蓄積
  • Author(s): 河本恭裕
  • Organizer: 第53会日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] パーキンソン病患者の中脳黒質のLewy小体におけるapoptosome関連タンパク質の集積
  • Author(s): 河本恭裕
  • Organizer: 第54会日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] 脳幹型および皮質型Lewy小体におけるXIAPとHtrA2/Omiの共存
  • Author(s): 河本 恭裕
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
• [Presentation] Alzheimer病患者脳内におけるHtrA2/Omiの免疫組織化学的検討
  • Author(s): 河本 恭裕
  • Organizer: 第52回日本神経病理学会総会学術研究会
  • Place of Presentation: 京都