Molecular characterization and gene/regeneration therapy for amyotrophic lateral sclerosis
Project/Area Number |
18390257
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Okayama University |
Principal Investigator |
ABE Koji Okayama University, 大学院・医歯薬学総合研究科, 教授 (20212540)
|
Co-Investigator(Kenkyū-buntansha) |
KAMIYA Tatsushi 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70233955)
IKEDA Yoshio 岡山大学, 医学部・歯学部附属病院, 講師 (00282400)
TAKEHISA Yasushi 岡山大学, 医学部・歯学部附属病院, 助教 (00379752)
NAGAI Makiko 岡山大学, 医学部・歯学部附属病院, 助教 (80420488)
MURAKAMI Tetsuro 岡山大学, 医学部・歯学部附属病院, 助教 (70403475)
|
Project Period (FY) |
2006 – 2008
|
Project Status |
Completed (Fiscal Year 2008)
|
Budget Amount *help |
¥17,490,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2008: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2006: ¥6,700,000 (Direct Cost: ¥6,700,000)
|
Keywords | 神経分子病態学 / 筋萎縮性側索硬化症 / ALS / SOD1 / トランスジェニックマウス / 蛋白療法 / 遺伝子療法 / 再生療法 / TRIAD / protein transduction domain / TAT蛋白 / オートファジー / ミトコンドリア / 小胞体ストレス / 診断マーカー / 神経幹細胞 / 分化 / FGF2 / EGF |
Research Abstract |
筋萎縮性側索硬化症(ALS)の病態を明らかにし、早期に有効な治療法を開発するため、ALSモデルマウスを用いてALS病態に関連する種々の分子の役割を明らかにした.また、ALS患者の脳脊髄液中に早期の確定診断を得るためのマーカーとなり得る分子があるかどうかを検討し、その候補を得た.また、再生療法と関連して、脊髄における内在性神経幹細胞の動態と各種神経栄養因子の神経幹細胞に対する活性化作用を明らかにした.さらにALSモデルマウスに対して、TAT融合蛋白の髄腔内持続投与による蛋白療法を開発し、良好な治療効果を得た.本研究による成果はALS患者の新規治療法の開発と臨床応用へ向けて、重要な知見を与えるものと考えられる.
|
Report
(4 results)
Research Products
(74 results)
-
[Journal Article] Progressive decrease in the level of YAPdeltaCs, prosurvival isoforms of YAP, in the spinal cord of transgenic mouse carrying a mutant SOD1 gene2009
Author(s)
Morimoto N, Nagai M, Miyazaki K, Kurata T, Takehisa Y, Ikeda Y, Kamiya T, Okazawa H, Abe K.
-
Journal Title
J Neurosci Res 87
Pages: 928-936
Related Report
Peer Reviewed
-
-
[Journal Article] Motor impairment ameliorated by L-DOPA administration in human alpha-synuclein A30P+A53T transgenic mice with alpha-synuclein pathology2009
Author(s)
Ikeda M, Kawarabayashi T, Harigaya Y, Sasaki A, Yamada S, Matsubara E, Murakami T, Tanaka Y, Kurata T, Wuhua X, Ueda K, Kuribara H, Ikarashi Y, Nakazato Y, Okamoto K, Abe K, Shoji M.
-
Journal Title
Brain Res 1250
Pages: 232-241
Related Report
Peer Reviewed
-
-
-
[Journal Article] Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis2008
Author(s)
Ohta Y, Kamiya T, Nagai M, Nagata T, Morimoto N, Miyazaki K, Murakami T, Kurata T, Takehisa Y, Ikeda Y, Asoh S, Ohta S, Abe K.
-
Journal Title
J Neurosci Res 86
Pages: 3028-3037
Related Report
Peer Reviewed
-
-
[Journal Article]2008
Author(s)
Kurata T, Hayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Kawarabayashi T, Takao Y, Ohta T, Harigaya Y, Manabe Y, Kamiya T, Shoji M, Abe K.
-
Journal Title
Neurol Res 30
Pages: 860-867
Related Report
Peer Reviewed
-
[Journal Article] Reduction of cerebrainfarction in rats by biliverdin associated with amelioration of oxidative stress2008
Author(s)
Deguchi K, Hayashi T, Nagotani S, Sehara Y, Zhang H, Tsuchiya A, Ohta Y, Tomiyama K,Morimoto N, Miyazaki M, Huh NH, Nakao A, Kamiya T, Abe K.
-
Journal Title
Brain Res 1188
Pages: 1-8
Related Report
Peer Reviewed
-
[Journal Article] Gelatin-siloxane hybrid scaffolds with vascular endothelial growth factor induces brain tissue regeneration2008
Author(s)
Zhang H, Kamiya T, Hayashi T, Tsuru K, Deguchi K, Lukic V, Tsuchiya A, Yamashita T, Hayakawa S, Ikeda Y, Osaka A, Abe K.
-
Journal Title
Curr Neurovasc Res 5
Pages: 112-117
Related Report
Peer Reviewed
-
[Journal Article] Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls2008
Author(s)
Xu W, Kawarabayashi T, Matsubara E, Deguchi K, Murakami T, Harigaya Y, Ikeda M, Amari M, Kuwano R, Abe K, Shoji M.
-
Journal Title
Brain Res 1219
Pages: 169-179
Related Report
Peer Reviewed
-
-
-
[Journal Article] Differentiation of PA from early PSP with different patterns of symptomsand CBF reduction.2008
Author(s)
Kurata T, Hayashi T. Murakaoi T, Miyazaki K, Morinoto N, Ohta Y. Takehisa Y, Nagai M, Kanarabayashi T, Takao Y. Ohta. T, Harigaya Y. Manabe Y, Kamiya T. Shoji M, Abe K.
-
Journal Title
Neurol Res. 30
Pages: 860-867
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Increased autophagy in transgenic mice with a G93A mutant SOD1 gene2007
Author(s)
Morimoto N, Nagai M, Ohta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K.
-
Journal Title
Brain Res 1167
Pages: 112-117
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Enhanced accumulation ophosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor protein and presenilin-12007
Author(s)
Kurata T, Kawarabayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai M, Ikeda M, Matsubara E, Westaway D, Hyslop PS, Harigaya Y, Kamiya T, Shoji M, Abe K.
-
Journal Title
J Neurosci Res 85
Pages: 2246-2252
Related Report
Peer Reviewed
-
[Journal Article] Two cases of spinocerebellar ataxiaccompanied by involvement of the skeletal motor neuron system and bulbar palsy2007
Author(s)
Ohta Y, Hayashi T, Nagai M, Okamoto M, Nagotani S, Nagano I, Ohmori N, TakehisaY, Murakami T, Shoji M, Kamiya T, and Abe K.
-
Journal Title
Intern Med 46
Pages: 751-755
Related Report
Peer Reviewed
-
[Journal Article] Increased autophagy in transgenic mice with a G93A mutant SOD1 gene.2007
Author(s)
Morimoto N, Nagai M, Ohta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K
-
Journal Title
Brain Res 1167
Pages: 112-117
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Enhanced accumulation of phosphorylated alpha-synuclein in double transgenic mice expressing mutant beta-amyloid precursor prtotein and presenilin-1.2007
Author(s)
Kurata T, Kawarabayashi T, Murakami T, Miyazaki K, Morimoto N, Ohta Y, Takehisa Y, Nagai N, Ikeda M, Natsubara E, Westaway D, Hyslop PS, Harigaya Y, Kamiya T, Shoji M, Abe K
-
Journal Title
J Neurosci Res 85
Pages: 2246-2252
Related Report
Peer Reviewed
-
[Journal Article] Two cases of spinocerebellar ataxia accompanied by involvement of the skeletal motor neuron system and bulbar palsy.2007
Author(s)
Ohta Y, Hayashi T, Nagai M, Okamoto M, Nagotani S, Nagano I, Ohmori N, Takehisa Y, Murakami T, Shoji M, Kamiya T, and Abe K
-
Journal Title
Intern Med 46
Pages: 751-755
NAID
Related Report
Peer Reviewed
-
-
[Journal Article] Implantation of a new porous gelatin-siloxane hybrid into a brain lesion as a potential scaffold for tissue regeneration2006
Author(s)
Deguchi K, Tsuru K, Hayashi T, Takaishi M, Nagahara M, Nagotani S, Sehara Y, Jin G, Zhang H, Hayakawa S, Shoji M, Miyazaki M, Osaka A, Huh NH, Abe K.
-
Journal Title
J Cereb Blood Flow Metab 26
Pages: 1263-1273
Related Report
Peer Reviewed
-
-
-
[Journal Article] Subventricular zone-derived neuroblasts migrate and differentiate intomature neurons in the post-stroke adult striatum2006
Author(s)
Yamashita T, Ninomiya M, Hernandez AcosP, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, K.
-
Journal Title
J Neurosci 26
Pages: 6627-6636
Related Report
Peer Reviewed
-
[Journal Article] Cortical neuronal and glial pathology TgTauP301L transgenic mice : neuronal degeneration, memory disturbance, and phenotypic variation2006
Author(s)
Murakami T, Paitel E, Kawarabayashi T, Ikeda M, Chishti MA, Janus C, Matsubara E, Sasaki A, Kawarai T, Phinney AL, Harigaya Y, Horne P, Egashira N, Mishima K, Hanna A, Yang J, Iwasaki K, Takahashi M, Fujiwara M, Ishiguro K, Bergeron C, Carlson GA, Abe K, Westaway D, St George-Hyslop P, Shoji M.
-
Journal Title
Am J Pathol 169
Pages: 1365-1375
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
[Presentation] A Rho-kinase inhibitor prevents apoptosis-induced neuronal cell death following transient focal ischemia in rats2008
Author(s)
Kamiya T, Inaba T, Nito C, Ueda M, Kato K, Suda S, Hayashi T, Deguchi K, Yamashita T, Sehara Y, Tsuchiya A, Han Zhe Zhang, V, Katayama Y, Abe K.
Organizer
6th World Stroke Congress
Place of Presentation
Vienna, Austria
Related Report
-
[Presentation] Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidstress2008
Author(s)
Deguchi K, Hayashi T, Nagotani S, Sehara Y, HanZhe Zhang, Tsuchiya A, Ohta Y, TomiyamK, Morimoto N, Miyazaki M, Nam-ho Huh, Nakao A, Kamiya T, Abe K.
Organizer
6th World Stroke Congre
Place of Presentation
Vienna, Austria
Related Report
-
-
[Presentation] Preventionof neuronal damage by calcium channel blockers with antioxidative effects aftertransient focal ischemia in rats2008
Author(s)
Violeta Lukic-Panin, Kamiya T, HanZhe Zhang, Hayashi T, Tsuchiya A, Sehara Y, Deguchi K, Yamashita T, Abe K.
Organizer
5th International Conference on Neuroprotection and Neurorepair, CerIschemia and Stroke
Place of Presentation
Magdeburg, Germany
Related Report
-
-
-
[Presentation] Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidative stress.2008
Author(s)
Deguchi K. Hayashi T, Hagotani S, Sehara Y, Han Zhe Zhang, Tsuchiya A. Obta Y, Tomiyama K, Morimoto N. Kiyazaki M, Nai-ho Huh. Kakao A, Kaniya T, Abe K.
Organizer
6th World Stroke Congress
Place of Presentation
Vienna, Austria
Related Report
-
-
-
-
-
[Presentation] Intrathecal injection of EGF and FGF2 promotes proliferation of neural precursor cells in the spinal cords owith mutant human SOD1 gene2007
Author(s)
Ohta Y, Nagai M, Nagata T, Murakami T, Nagano I, Narai H, Kurata T, Shiote M, Shoji M, and Abe K.
Organizer
12thInternational Congress of World Muscle Society
Place of Presentation
Naxos, Italy
Related Report
-
[Presentation] Enhanced accumulation of phosphorylated α-synuclein in transgenic mice eAPP and PS-12007
Author(s)
Kurata T, Kawarabayashi T, Murakami T, Morimoto N, Ota Y, Ikeda Y, Nagai M, Takehisa Y, Matsubara E, David Westaway, Peter St. George Hyslop, Harigaya Y, T, Shoji M, and Abe K.
Organizer
13th Congress of International Psychogeriatric
Place of Presentation
Osaka, Japan
Related Report
-
[Presentation] Beneficial Effectsof Intrathecal Administration in Patientswith Amyotrophic Lateral Screlosis2007
Author(s)
Morimoto N, Nagano I, Murakami T, Nagai M, Shiote M, Ohta Y, Morimoto M, Takehisa Y, Kamiya T, and Abe K.
Organizer
The 23rd International Symposium on CereBlood Flow, Metabolism and ThInternational Conference on Quantification of Brain Funct
Place of Presentation
Osaka, Japan
Related Report
-
-
[Presentation] Dysfunction ofmitochondrial oxidative phosphorylation in ALS rat model2007
Author(s)
Nagai M, Murakami T, Ohta Y, Takehisa Y, Morimoto N, Miyazaki K, Kurata T, Kamiya T, Abe K, and Przedborski S.
Organizer
The 23rd InternatSymposium on Cerebral Blood Flow, Metabolism and The 8th International Conference on Quantification of Brain Functio with PET
Place of Presentation
Osaka, Japan
Related Report
-
-
[Presentation] Intrathecal injection of EGF and FGF2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene.2007
Author(s)
Ohta Y, Nagai M, Nagata T, Murakami T, Nagano I, Narai H, Kurata T, Shiote M, Shoji M, and Abe K
Organizer
12th International Congress of World Muscle Society
Place of Presentation
Naxos, Italy
Related Report
-
[Presentation] Enhanced accumulation of phosphorylated α-synuclein in transgenic mice expressing APP and PS-1.2007
Author(s)
Kurata T, Kawarabayashi T, Nurakami T, Morimoto N, Ota Y, Ikeda Y, Nagai N, Takehisa Y, Matsubara E, David Westaway, Peter St. George Hyslop, Harigaya Y, Kamiya T, Shoji M, and Abe K
Organizer
13th Congress of International Psychogeriatric Association
Place of Presentation
Osaka, Japan
Related Report
-
[Presentation] Beneficial Effects of Intrathecal Administration in Patients with Amyotrophic Lateral Screlosis.2007
Author(s)
Morimoto N, Nagano I, Murakami T, Nagai M, Shiote M, Ohta Y, Morimoto M, Takehisa Y, Kamiya T, and Abe K
Organizer
The 23rd International Symposium on Cerebral Blood Flow, Metabolism and The 8th International Conference on Quantification of Brain Function with PET
Place of Presentation
Osaka, Japan
Related Report
-
-
[Presentation] Dysfunction of mitochondrial oxidative phosphorylation in ALS rat model.2007
Author(s)
Nagai M, Murakami T, Ohta Y, Takehisa Y, Morimoto N, Miyazaki K, Kurata T, Kamiya T, Abe K, and Przedborski S
Organizer
The 23rd International Symposium on Cerebral Blood Flow, Metabolism and The 8th International Conference on Quantification of Brain Function with PET
Place of Presentation
Osaka, Japan
Related Report
-
-
-
[Presentation] Accumulation of Parkinson's-disease-related moleculLewy bodies and glial cytoplasmic inclusions2006
Author(s)
Murakami T, Imai Y, Inoue H, Kawarabayashi T, Nagai M, Kurata T, Takehisa Y, Harig Y, Shoji M, Takahashi Y, Harigaya Y, Shoji M, Takahashi R, and Abe K.
Organizer
10^<th> International Congress of Parkinson's Disease and Movement
Place of Presentation
Kyoto, Japan
Related Report
-
[Presentation] Enhanced accumulation of phosphorylated α-synuclein in transgenic mice expressingAPP and PS-12006
Author(s)
Kurata T, Kawarabayashi T, Murakami T, Miyazaki K, Morimoto N, Ota Y, Takehisa Y, Nagai M, Ikeda M, Matsubara E, Westaway D, St George Hyslop P, Harigaya Y, Kamiya T, Shoji M, and Abe K.
Organizer
The 6^<th> Annual Meetingof International Collegeof Geriatric Psychoneuropharmacology
Place of Presentation
Hiroshima, Japan
Related Report
-
-
-
-