1992 Fiscal Year Annual Research Report

クロイツフェルト・ヤコブ病プリオン蛋白のシナプス内局在の同定

Research Project

Project/Area Number	03454171
Research Institution	KYUSHU UNIVERSITY
Principal Investigator	北本哲之九州大学, 医学部, 講師 (20192560)
Co-Investigator(Kenkyū-buntansha)	立石潤九州大学, 医学部, 教授 (70033305)
Keywords	クロイツフェルト・ヤコブ病 / シナプス / プリオン蛋白 / プリオン蛋白遺伝子
Research Abstract	クロイツフェルト・ヤコブ病(以下CJDと略す)の原因因子としてプリオン仮説が提唱されている。昨年度開発した加水分解オートクレーブ法ににより、プリオン蛋白遺伝子の野生型をもつCJD患者では、シナプスに異常プリオン蛋白が沈着していることを報告したが、今年度はプリオン蛋白遺伝子解析として、PCR(polymerase chain reaction)法によるダイレクトシークエンスを行い新しい変異型を5種みいだした。コドン105の変異は、日本の家族性痴呆で認められ、クル斑を主体とし、シナプスをおかすことは稀である。以前は、家族性痙性麻痺と診断されていた。コンド145の変異は、アルツハイマー病型の臨床症状を呈し、蛋白学的にはストップコドンとなり、C末約100コのアミノ酸のない変異型プリオン蛋白より構成されるクル斑が存在し、シナプスには決着しない。コドン180、232の変異は、CJD患者で認められ、この変異では今のところクル斑はなく、主にシナプスをおかす。最後に、96bpの挿入変異を証明した。この挿入変異は、クル斑を形成し、シナプスは軽度に沈着するのみであった。この2年間にわたる本研究では、新たに異常のプリオン蛋白の沈着部位として、中枢神経系のシナプス、リンパ系の樹状細胞を明らかとしたことと、ヒトプリオン蛋白遺伝子の変異を新たに5種類発見し、それぞれ、プリオン蛋白の沈着型として、シナプス型、クル斑型に分類した。シナプス型では、臨床経過が長く、ゆっくりした経過をとることより、異常プリオン蛋白の沈着形成が直接臨床病型に影響を及ぼすことを明らかとした。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Tateishi,J.: "Creutzfeldt-Jakob disease with amyloid angiopathy:diagnosis by immunological analyses and transmission experiments." Acta Neuropathol.83. 559-563 (1992)
[Publications] Kitamoto,T.: "Abnormal isoform of prion protein accumulates in the synaptic structures in patients with Creutzfeldt-Jakob disease." Am.J.Pathol. 140. 1285-1294 (1992)
[Publications] Miyazono,M.: "Colocalization of prion protein and β protein in the same amyloid plaque in patient with Gerstmann-Straussler syndrome." Acta Neuropathol.83. 333-339 (1992)
[Publications] Muramoto,T.: "The sequential development of abnormal prion protein accumulations in mive with Creutzfeldt-Jakob disease." Am.J.Pathol.140. 1411-1420 (1992)
[Publications] Ohgami,T.: "Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions." Neurosci.Lett.136. 75-78 (1992)
[Publications] Miyazono M,: "Creutzfeldt-Jakob disease with codon 129 polymorphism(Valine):a comparative study of patients with codon 102 point mutation or without mutation." Acta Neuropathol.84. 359-354 (1992)
[Publications] Kitamoto,T.: "The primary structure of the prion protein influences the distribution of abnormal prion protein in the central nervous system." Am.J.Pathol.141. 271-277 (1992)
[Publications] Tranchant,C.: "Gerstmann-Straussler-Scheinker disease in an Alsatian family: clinical and genetic study." J.Neurol.Neurosurg. Psychiat.55. 185-187 (1992)
[Publications] Shin,R.-W.: "Massive accumulation of modified tau and severe depletion of normal tau characterize the cerebral cortex and white matter of Alzheimer's disease." Am.J.Pathol.140. 937-945 (1992)
[Publications] Muramoto,T.: "Successful transmission of Creutzfeldt-Jakob disease from human to mouse verified by prion protein accumu-lation in mouse brains." Brain Res.599. 309-316 (1992)
[Publications] Muramoto,T.: "The coexistence of Alzheimer's disease and Creutzfeldt-Jakob disease in a patient with dementia of long duration" Acta Neuropathol.84. 686-689 (1992)
[Publications] Kitamoto,T.: "Novel missense variants of prion protein in Creutzfeldt-Jakob disease of Gerstmann-Straussler syndrome." Biochem.Biophys.Res.Commun.
[Publications] Tateishi,J.: "Prion disease of humans and animals" ELLIS HORWOOD, 9 (1992)
[Publications] Kitamoto,T.: "Alzheimer's disease:Advances in Clinical and Basic" in press, (1992)
[Publications] Kitamoto,T.: "Handbook of cerebral disease." (1992)

1992 Fiscal Year Annual Research Report

クロイツフェルト・ヤコブ病プリオン蛋白のシナプス内局在の同定

Principal Investigator

北本 哲之 九州大学, 医学部, 講師 (20192560)

Research Products

[Publications] Tateishi,J.: "Creutzfeldt-Jakob disease with amyloid angiopathy:diagnosis by immunological analyses and transmission experiments." Acta Neuropathol.83. 559-563 (1992)

[Publications] Kitamoto,T.: "Abnormal isoform of prion protein accumulates in the synaptic structures in patients with Creutzfeldt-Jakob disease." Am.J.Pathol. 140. 1285-1294 (1992)

[Publications] Miyazono,M.: "Colocalization of prion protein and β protein in the same amyloid plaque in patient with Gerstmann-Straussler syndrome." Acta Neuropathol.83. 333-339 (1992)

[Publications] Muramoto,T.: "The sequential development of abnormal prion protein accumulations in mive with Creutzfeldt-Jakob disease." Am.J.Pathol.140. 1411-1420 (1992)

[Publications] Ohgami,T.: "Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions." Neurosci.Lett.136. 75-78 (1992)

[Publications] Miyazono M,: "Creutzfeldt-Jakob disease with codon 129 polymorphism(Valine):a comparative study of patients with codon 102 point mutation or without mutation." Acta Neuropathol.84. 359-354 (1992)

[Publications] Kitamoto,T.: "The primary structure of the prion protein influences the distribution of abnormal prion protein in the central nervous system." Am.J.Pathol.141. 271-277 (1992)

[Publications] Tranchant,C.: "Gerstmann-Straussler-Scheinker disease in an Alsatian family: clinical and genetic study." J.Neurol.Neurosurg. Psychiat.55. 185-187 (1992)

[Publications] Shin,R.-W.: "Massive accumulation of modified tau and severe depletion of normal tau characterize the cerebral cortex and white matter of Alzheimer's disease." Am.J.Pathol.140. 937-945 (1992)

[Publications] Muramoto,T.: "Successful transmission of Creutzfeldt-Jakob disease from human to mouse verified by prion protein accumu-lation in mouse brains." Brain Res.599. 309-316 (1992)

[Publications] Muramoto,T.: "The coexistence of Alzheimer's disease and Creutzfeldt-Jakob disease in a patient with dementia of long duration" Acta Neuropathol.84. 686-689 (1992)

[Publications] Kitamoto,T.: "Novel missense variants of prion protein in Creutzfeldt-Jakob disease of Gerstmann-Straussler syndrome." Biochem.Biophys.Res.Commun.

[Publications] Tateishi,J.: "Prion disease of humans and animals" ELLIS HORWOOD, 9 (1992)

[Publications] Kitamoto,T.: "Alzheimer's disease:Advances in Clinical and Basic" in press, (1992)

[Publications] Kitamoto,T.: "Handbook of cerebral disease." (1992)

北本哲之九州大学, 医学部, 講師 (20192560)