The Association of AGEs (Advanced Glycation End product) and oxoaldehydes with spinal motor neuronal death
| Project/Area Number |
14570574
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KIKUCHI Seiji Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (10271660)
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| Co-Investigator(Kenkyū-buntansha) |
森若 文雄 北海道大学, 大学院・医学研究科, 助教授 (30142722)
田代 邦雄 北海道大学, 大学院・医学研究科, 教授 (90002154)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Amyotrophic lateral sclerosis / Advanced glycation end product / Spinal motor neuron / Carboxymethyl lysine / 運動ニューロン / ユビキチン・プロテアソーム系 / 分子生物学 / 脊髄器官培養 |
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| Research Abstract |
<INTRODUCION>Amyotrophic lateral sclerosis (ALS) is one of the major neurodegenerative diseases, which presents generalized progressive muscular atrophy and weakness. Specific loss of motor neurons and abnormal accumulation of proteins in remained motor neurons are critical features in pathology. Accumulated proteins are post-translational modified by oxidation, nitration, ubiquitination, and so on. Among many kinds of modification, we focused glycation. Advanced glycation end products (AGEs) are produced by non-enzymatic glycation and involved in retinal, renal and neuronal complication in diabetic patients. Recently, they were reported to deposit in the brain of Alzheimer's disease.
<MEIHODS>1.we investigated spinal cord of autopsied ALS patients and disease controls with several kinds of anti-AGE antibody. 2.Using primary cultures and organotypic slice cultures prepared from rat spinal cords, the change of post translational modification were examined after exposure to several cytotoxic agents.
<RESULTS>1.Some atrophied spinal motor neurons and microglias in ALS patients were positive with anti-carhoxymethyl lysine (CML) antibody. Non-CML AGES were also positive in axonal spheroids and microglias. They co-existed with SOD1 and neurofilaments. There was not any positive cell in control cases nor non-motor neurons in ALS. 2.The proteasome inhibitory agents induced relatively selective death of motor neuron in primary cultures. They increased protein ubiquitination and CML-modification.
<DISCUSSION>CNL was frequently used to investigate glycation. However, currently it was also revealed that it comes from lipid peroxidation. The anti-AGE antibody we used in this study doesn't recognize CML. Then our results show the presence of glycation in evidence. The substrate for glycation is unknown. SOD1, the mutant protein of familial ALS (ALS1) and neurofilaments are probable substrates, and their abnormal modification might induce protease resistant protein accumulation.
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Report
(4 results)
Research Products
(44 results)
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[Journal Article] Neurotoxicity of acetaldehyde-derived advanced glycation end products for cultured cortical neurons2003
Author(s)
Takeuchi M, Watai T, Sasaki N, Choei H, Iwaki M, Ashizawa T, Inagaki Y, Yamagishi S, Kikuchi S, Peter Riederer, Saito T, Richard Bucara, Kameda Y
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Journal Title
J Neuropathol Exp Neurol 62
Pages: 486-496
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques2002
Author(s)
Sasaki N, Takeuchi M, Chowei H, Kikuchi S, Hayashi Y, Nakano N, Ikeda H, Yamagishi S, Kitamoto T, Saito T, Makita Z
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Journal Title
Neurosci Lett 326
Pages: 117-120
Description
「研究成果報告書概要(欧文)」より
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