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1999 Fiscal Year Final Research Report Summary

Glycation and AGEs in motor neurons - synergism with oxidative stress -

Research Project

Project/Area Number 10670569
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KIKUCHI Seiji  Hokkaido Univ., School of Medicine, Inst., 医学部, 助手 (10271660)

Co-Investigator(Kenkyū-buntansha) MORIKAWA Fumio  Hokkaido Univ., School of Medicine, Asso. Pro., 医学部, 助教授 (30142722)
TASHIRO Kunio  Hokkaido Univ., School of Medicine, Pro., 医学部, 教授 (90002154)
Project Period (FY) 1998 – 1999
KeywordsALS / glycation / oxidative stress / motor neuron / advanced glycation end products (AGES)
Research Abstract

Glycation of proteins, through the reversible synthesis of Schiff bases and via Amadori products, leads to the production of advanced glycation end products (AGEs). Glycation is recently suggested to be involved in neurodegenerative diseases such as Alzheimer's disease.
Methylglyoxal (MG) and 3-deoxyglucosone (3DG), both of which are known to accelerate the production of AGEs, have toxic effects on cultured cortical and spinal neurons in concentration dependent manner. Cultured spinal motor neurons were more susceptible than those of cultured spinal non-motor neurons and cortical neurons. Reactive oxygen species were recognized to be concerned in the toxicity, and N-acetylcysteine(NAC, glutathione precursor) showed the protective effect. The protective effect of NAC was remarkable in spinal motor neurons, suggesting the deficiency of glutathione system in them. Since the level of glutathione was almost the same in motor and non-motor neurons, the deficiency of glutathione system in motor neurons is supposed to be derived from the inefficient metabolism and availability of glutathione.
The early stage products of glycation, such as 1-hexitollysine and fructated lysine, and AGES such as CML and nonCML AGEs were demonstrated in the spinal cord of ALS. CML AGE was shown in the soma of atrophic motor neurons and glia. CML AGE can be thought to reflect the lipid peroxidation. It was supported by the notion that the donor of nitric oxide increased the production of CML but not non-CML AGEs in cultured neurons. The early stage products of glycation, such as 1-hexitollysine and fructated lysine were mainly located in the spheroids, the constituents of which can be thought to be neurofilaments. As the evidence of the further reaction of glycation leading to AGEs, non-CML AGE was shown in soma of atrophic motor neurons as well as in the spheroids.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Shinpo K. Kikuchi S. et al.: "Protective effect of the THF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons"Brain Res. 819. 170-173 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kikuchi S. Shinpo K. et al.: "Neurotoxicity of Methylglyoxal and 3-Deoxyglucosone on cultured cortical neurons. Synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases"J Neurosci Res. 57. 280-289 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kikuchi S. Ogata A. et al.: "Detection of an Amadori product, 1-hexitol-lysine, in the anterior horn of the ALS and SBMA spinal cord. Evidence for early involvement of glycation in motoneuron diseases"Acta Neuropathol. 99. 63-66 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinpo K. Kikuchi S. et al.: "Selective vulnerability of spinal neurons to reactive dicarbonyl compounds, intermediate products of glycation, in vitro implication of inefficient glutathione system in spinal motor neurons"Brain Res. 57(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinpo K. Kikuchi S et al.: "Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons."Brain Res. 819. 170-173 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kikuchi S. Shinpo K et al.: "Neurotoxicity of Methylglyoxal and 3-Deoxyglucosone on cultured cortical neurons. Synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases."J Neurosci Res. 57. 280-289 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kikuchi S. Ogata A et al.: "Detection of an Amadori product. 1-hexitol-lysine, in the anterior horn of the ALS and SBMA spinal cord. Evidence for early involvement of glycation in motoneuron diseases."Acta Neuropathol. 99. 63-66 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinpo K. Kikuchi S et al.: "Selective vulnerability of spinal neurons to reactive dicarbonyl compounds. Intermediate products of glycation. In vitro - implication of inefficient glutathione system in spinal motor neurons - ."Brain Res. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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