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1999 Fiscal Year Final Research Report Summary

Molecular mechanism and gene therapy of familial ALS

Research Project

Project/Area Number 09470151
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOkayama University (1998-1999)
Tohoku University (1997)

Principal Investigator

ABE Koji  Okayama University Medical School, Professor, 医学部, 教授 (20212540)

Project Period (FY) 1997 – 1999
KeywordsALS / SOD / transgenic mice / gene therapy
Research Abstract

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder affecting predominantly motor neurons in the central nervous system. There has been no effective treatment, and the duration is usually 2-5 years. About 5-10% of ALS is thought to be familial (FALS) with an autosomal dominant inheritance, or less often recessive.
We report here seven FALS families associated with four different missense mutations of the Cu/Zn SOD gene (D6F, H46R, L84V, A90V, I104F, S134N, and V148I), and each family has unique clinical characteristics. Protein tyrosin nitration of spinal motor neurons was found in ALS patients, but not in control subjects. With transgenic mice of G93A Cu/Zn SOD gene mutation, we found early and selective impairment of fast axonal transport by ligation of sciatic nerves. Furthermore, immunoreactivity of cell survival signal such as Akt and PI3K showed early decrease in spinal motor neurons, but immunoreactivities for cell death signals such as caspases or TUNEL was not positive until the advance stage of motor neuron death, indicating a critical imbalance of cell survival and death signals in dying motor neurons. In addition, -mediated Lace gene was effectively transferred and expressed in muscles and spinal motor neurons in transgenic symptomatic mice, and established a therapic basis for human ALS patients.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Warita et al.: "Selective impairment of fast antegrade axonal transport in the peripheral nerves of presymptomatic transgenic mice with a G93A mutant 5091"Brain Res.. 819. 120-131 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda et al.: "HSP70 and HSC70 mRNA induction in the brains, hearts, and livers of nonatal rats after hypoxic stress"Am. J. Obstet, Gynecol.. 180. 457-461 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi et al.: "Expression of angiogenic factors in rabbit spinal cord after transient ischemia of rabbit"Neuropathol. Appl. Neurobiol.. 25. 63-71 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe et al.: "Neurons : necrotic vs apoptotic changes"Cerebral. Ischemia. 1. 217-232 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Manabe et al.: "Enhanced FOS expression in rat limbar spinal cord cultured with CSF from patients with ALS"Neurol. Res.. 21. 309-312 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitagawa et al.: "Adenovirus-mediated gene transfer of GONF prevents ischemic brain injury after transient MCA occlusion in rats"J. Cereb. Blood Flow Metabol.. 19. 1336-1344 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 阿部 康二: "脊髄小脳変性症の臨床"阿部康二 編著(新興医学出版社). 201 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Warita, Y. Itoyama, and K. Abe.: "Selective impairment of fast anterograde axonal transport in the peripheral nerves of asymptomatic transgenic mice with a G83A mutant SOD1 gene"Brain Res.. 819. 120-131 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Ikeda, K. Abe, A. Ota, and T. Ikenoue.: "HSP70 and HSC70 mRNA induction in the brains, hearts, and livers of neonatal rats after hypoxic stress"Am. J. Obstet. Gynecol.. 180. 457-461 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Hayashi, M. Sakurai, K. Abe, T. Sadahiro, H. Tabayashi, and Y. Itoyama: "Expression of angiogenic factors in rabbit spinal cord after transient ischaemia"Neuropathol. Appl. Neurobiol.. 25. 63-71 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Abe: "Neurons : necrotic vs apoptotic changes"Cerebral Ischemia. 1. 217-232 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Manabe, K. Kashihara, Y. Shiro, T. shohmori, and K. Abe: "Enhanced Fos expression in rat lumber spinal cord cultured with cerebrospinal fluid from patients with ALS"Neurol. Res.. 21. 309-312 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Kitagawa, C. Sasaki, K. Sakai, A. Mori, Y. Mitsumoto, T. Mori, Y. Fukuchi, Y. Setoguchi, and K. Abe: "Adenovirus-mediated gene transfer of GDNF prevents ischemic brain injury after transient MCA occulusion in rats"J. Cereb. Blood Flow Metabol.. 19. 1336-1344 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Abe ed.: "Clinical management of spinocerebellar ataxia"Sinko Medical Publisher (Tokyo, Japan). 201 (1999)

    • 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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