Development of next-generation therapy based on comprehensive molecular pathology of neurodegenerative diseases
Project/Area Number |
17H04196
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Okayama University |
Principal Investigator |
Abe Koji 岡山大学, 医歯薬学総合研究科, 教授 (20212540)
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Co-Investigator(Kenkyū-buntansha) |
太田 康之 岡山大学, 大学病院, 講師 (20746854)
山下 徹 岡山大学, 医歯薬学総合研究科, 講師 (60644408)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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Keywords | 神経変性疾患 / ALS / アルツハイマー型認知症 / フリーラジカル / 酸化ストレス / 核細胞質輸送障害 |
Outline of Final Research Achievements |
By using a AD model mouse with cerebral blood flow hypoperfusion established recently revealed that edaravone treatment can significantly improve motor and cognitive dysfunction. We also established novel ALS mice model that visualize oxidative stress, and found that the expression of oxidative stress in the spinal cord and lower limb muscles was enhanced early in the onset of ALS. Blood flow and glucose metabolism in the spinal cord of ALS patients were evaluated by PET examination, and it was observed that glucose metabolism was abnormally elevated in the ALS cervical spinal cord without increase in blood flow. Furthermore, as a result of exploratory research using a new peptideme analysis technology, 4 types of peptides specific to mild cognitive impairment (MCI) and Alzheimer's disease (AD) were found.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、神経変性疾患共通(普遍性のある)の分子病態解明のため、酸化ストレスと核細胞質輸送障害、蛋白ゲル化異常の相互関与に注目した挑戦的かつ総合的研究である。課題申請者らが発見したAsidanの病態も、欧米で特に多いC9orf72遺伝子異常との類似点から、神経変性疾患共通病態への関与に注目し解明を目指しており、本研究成果は国際的にも重要なインパクトを与えうる。本研究では神経変性疾患共通の分子病態解明および新規治療法開発につながる可能性があり、この課題研究から得られた成果は、将来的には神経変性疾患共通の根本的治療法の確立に道を開き、国際的にも波及効果の高い貢献をもたらすものと考えられる。
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology.2020
Author(s)
Abe K, Shang J, Shi X, Yamashita T, Hishikawa N, Takemoto M, Morihara R, Nakano Y, Ohta Y, Deguchi K, Ikeda M, Ikeda Y, Okamoto K, Shoji M, Takatama M, Kojo M, Kuroda T, Ono K, Kimura N, Matsubara E, Osakada Y, Wakutani Y, Takao Y, Higashi Y, Asada K, Senga T, Lee LJ, Tanaka K
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Journal Title
J Alzheimers Dis.
Volume: 73(1)
Issue: 1
Pages: 217-227
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis.2018
Author(s)
Ohta Y, Nomura E, Shang J, Feng T, Huang Y, Liu X, Shi X, Nakano Y, Hishikawa N, Sato K, Takemoto M, Yamashita T, Abe K.
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Journal Title
J Neurosci Res.
Volume: Epub ahead of print
Issue: 5
Pages: 607-619
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Potential multisystem degeneration in Asidan patients.2017
Author(s)
Ohta Y, Yamashita T, Hishikawa N, Sato K, Matsuzono K, Tsunoda K, Hatanaka N, Takemoto M, Takemi T, Takamatsu K, Abe K
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Journal Title
J Neurol Sci.
Volume: 373
Pages: 216-222
DOI
Related Report
Peer Reviewed
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[Journal Article] Behavioral and affective features of amyotrophic lateral sclerosis patients.2017
Author(s)
Ohta Y, Sato K, Takemoto M, Takahashi Y, Morihara R, Nakano Y, Tsunoda K, Nomura E, Hishikawa N, Yamashita T, Abe K
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Journal Title
J Neurol Sci.
Volume: 381
Pages: 119-125
DOI
Related Report
Peer Reviewed
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[Journal Article] Aberrant distributions of nuclear pore complex proteins in ALS mice and ALS patients.2017
Author(s)
Shang J, Yamashita T, Nakano Y, Morihara R, Li X, Feng T, Liu X, Huang Y, Fukui Y, Hishikawa N, Ohta Y, Abe K
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Journal Title
Neuroscience.
Volume: 350
Pages: 158-168
DOI
Related Report
Peer Reviewed
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[Presentation] Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-22019
Author(s)
Yamashita T, Morihara R, Kono S, Shang J, Nakano Y, Sato K, Hishikawa N, Ohta Y, Heitmeier S, Perzborn E, Abe K
Organizer
BRAIN & BRAIN PET 2019
Related Report
Int'l Joint Research
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[Presentation] Therapeutic effects of edaravone for enhanced oxidative stress in amyotrophic lateral sclerosis mice2019
Author(s)
Ohta Y, Nomura E, Shang J, Feng T, Nakano Y, Hishikawa N, Sato K, Takemoto M, Yamashita T, Omote Y, Abe K
Organizer
第60回日本神経学会学術大会
Related Report
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[Presentation] The pathological role of P413L variant chromogranin B as disease modifier in female amyotrophic lateral sclerosis.2018
Author(s)
Ohta Y, Soucy G, Phaneuf D, Audet JN, Gros-Louis F, Yamashita T, Sato K, Takemoto M, Hishikawa N, Julien JP, Abe K
Organizer
第59回日本神経学会学術大会
Related Report
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[Presentation] The role of variant chromogranin B as disease modifier in Japanese female amyotrophic lateral sclerosis.2017
Author(s)
Ohta Y, Soucy G, Phaneuf D, Audet JN, Gros-Louis F, Yamashita T, Sato K, Takemoto M, Hishikawa N, Julien JP, Abe K
Organizer
XXIII World Congress of Neurology
Related Report
Int'l Joint Research
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