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Biochemical study of glial cytoplasmic inclusions in multiple system atrophy brains

Research Project

Project/Area Number 05454258
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionUniversity of Tokyo, Faculty of medicine

Principal Investigator

NUKINA Nobuyuki  University of Tokyo (Medicene), assoc.Prof., 医学部(医), 助教授 (10134595)

Co-Investigator(Kenkyū-buntansha) IWATSUBO Takeshi  Dept of Pharmacy, Univ.of Tokyo, assoc.Prof., 薬学部, 客員助教授 (50223409)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsMultiple system atrophy / glial cytoplamic inclusion / DRPLA / Huntington disease / carboxyl methyl transferase / 多系統萎縮症 / glial cytoplasmic mclusion / αB-Crystallin / エビキチン / ユビキチン
Research Abstract

Glial cytoplamic inclusions (GCI) which appear in oligodendroglial cells are the main pathological feature of multiple system atrophy (MSA). In this study, to determine the main constituent of GCI we tried several assay methods of GCI including immunohistochemical methods and found that Gallyas staining is the best assay method of GCI.Using Gallyas staining we developed the partial purification method of GCI.Furthermore electron micrograph showed the fibrous GCI in the Triton insoluble GCI-enriched fraction which was also observed with Gallyas silver staining. Then we performed 2D gel analysis of the GCI-rich fraction. This analysis revealed the increased amount of the protein which showed MW22kD and p17.0-7.6 corresponding to alpha B-Crystallin. Immunoblots of 2D gel of that fraction were stained with anti-alpha B-Crystallin antibodies and with Gallyas silver staining. Anti-alpha B-Crystallin antibodies reacted with the spots which increased in GCI-enriched fraction corresponding to alpha B-Crystallin. Gallyas silver staining also stained these spots, suggesting that alpha B-Crystallin is one of the Gallyas reactive proteins. These results suggests that one of the main constituent of GCI is alpha B-Crystallin.
Furthermore anti-carboxyl methtltransferase antibodies stained GCI,suggesting that the racemization of those abnormal proteins occured in MSA brain.
We got several antibodies against the gene products of genetic neurological disorders to study the relationship between these protein and GCI.These antibodies detect abnormal gene products in trinucleotide diseases.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Iwatsubo,T. Hasegawa,M Ihara,Y.: "Neurunal and glial tau-positive inclusions in diverse neurologl diseases share common phosphorylation characteristics" Acta Neuropathol. 88. 129-136 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi,S. Kusunoki,S. Takatsu,R. Sunada,Y. Nukina,N. Tai,T. Kanazawa,I.: "Cerebellar atoxia and poly nearopathy in a patieut with IgM M-protein specific to the Cial(β1-3) Gal NAC epitope" J. Nenrol Sci. 126. 219-224 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yazawa,I. Nakina,N. Hashida,H. Goto,J. Yamada,M. Kanazawa,I.: "Abnormal gene product ideutified in hereditary dertatorulral-pallidolug sian atrophy(DRPLA) brain" Nature genetics. 10. 99-103 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ide,K,Nakina N,Masuda,N Goto,J Kanazawa,I: "Abrormal gere product idenfified in Huntingtons disease lymphocytes and brain" Biocham. Biophys. Res. Com.209. 1119-1125 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yazawa,I. Nakina,N Ichikawa,Y. Kanazawa,I: "Dentatorubral-pallicloluysian atrophy (DRPLA) prstein in the lymphoblastoid cells" Neurology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 貫名信行: "Neuropil threadsと痴呆" Demeutia. 8. 72-77 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Iwatsubo, T., Hasegawa, M.and Ihara, Y.: "Neuronal and glial tau-positive inchlusions in diverse neurologic diseases share common phosphorylation characteristics" Acta Neuropathol. 88. 129-136 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi, S., Kusunoki, S., Chiba, A., Takatsu, R., Sunada, Y., Nukina, N., Tai, T., Kanazawa, I.: "Cerebellar ataxia and polyneuropathy in a patient with IgM M-protein specific to the Gal (beta1-3) GalNAc epitope" J.Neurol.Sci. 126. 219-224 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yazawa, .I.Nukina, N., Hashida, H.Goto, J.Yamada, M.and Kanazawa, I.: "Abnormal gene product identified in hereditary dentatorubral-pallidolusian atrophy (DRPLA) brain" Nature genetics. 10. 99-103 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ide, K., Nukina, N., Masuda, N., Goto, J.and Kanazawa, I.: "Abnormal gene product identified in Huntington's disease lymphocytes and brain" Biochem.Biophys.Res.Com.209. 1119-1125 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yazawa, I., Nukina, N., Ichikawa, Y and Kanazawa, I.: "Dentatorbral-pallidoluysian atrophy (DRPLA) protein in the lymphoblastoid cells" Neurology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Iwatusbo,M.Hasegawa,Y.Ihara: "Neuronal and glial tan-positive inclusions in diverse neurologic disease" Acta Neuropathol. 88. 129-136 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Quan,N.Nukina,I.Kanazawa: "increased αB-Crystallin in glial cytoplasmic inclusion enriched fraction from multiple system atrophy brain" Society for Neuroscience Abstracts. 19. 835 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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