2002 Fiscal Year Final Research Report Summary
Analysis of the influence of residue 219 polymorphism of prion protein on human prion diseases
| Project/Area Number |
13670203
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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 |
Experimental pathology
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| Research Institution | Tohoku University |
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Principal Investigator |
MURAMOTO Tamaki Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学研究科, 助手 (40302096)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMOTO Tetsuyuki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20192560)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Creutzfeldt-Jakob disease / prion protein / polymorphism / dura mater grafting / abnormal isoform / subtype |
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| Research Abstract |
We investigated cases of dura grafl-associated Creutzfeldt-Jakob disease(CJD) and discovered that there are at least two subtypes of this entity that differ in clinical, pathological and biochemical characteristics. The clinical difference included the absence or relatively late appearance of myoclonus and characteristic eledroencephalographic changes, and slow transition into akinetic mutism in the subtype with prion protein plaques in comparison with that without plaques. The pathological difference included relatively milder brain atrophy and various unique morphologies of PrP depositions in the subtype with plaques. The biochemical difference was represented by a novel 11-12 kDa protease-resistant prion protein (PrP) fragment in brain tissue that is detected in the subtype without plaques but not in that with plaques. As for PrP gene, the subtypes were homogenous on polymorphism with the codons 129 Met/Met and 219 Glu/Glu homozygosity and without mutations.
To explore the association of the 11-12 kDa PrP fragment with other prion diseases, we investigated cases of sporadic, genetic and variant CJD and discovered that the PrP fragment is associaied with particular types or subtypes of these entities and is not found in unaffected subjects. It was detected not only in protease-resistant protein fractions but also untreated total lysate fractions from the affected brain tissues, and was as insoluble as the authentic abnormal isoform of PrP (PrPSc). These findings strongly argue that the PrP fragment is closely related to the pathogenesis of prion diseases. The patients were homozygous for the codon 219 Glu polymorphism.
Through all these studies, disease types with PrP plaques were unassociated with the PrP fragment, implicating shared mechanisms in their origins.
In these analyses, we also discovered that CJD associated with the codon 232 substitution of Argfor Met features in the deposition of the type 1 PrPSc in brain tissue.
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Research Products
(4 results)
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[Publications] Kitamoto T, Mohri S, Ironside JW, Miyoshi I, Tanaka T, Kitamoto N, Itohara S, Kasai N, Katsuki M, Higuchi J, Muramoto T, Shin R-W: "Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions"Biochem Biophys Res Commun. 294. 280-286 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kitamoto T, Mohri S, Ironside JW, Miyoshi I, Tanaka T, Kitamoto N, Itohara S, Kasai N, Katsuki M, Higuchi J, Muramoto T, Shin R-W: "Follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions"Biochem Biophys Res Commun. 294(2). 280-286 (2002)
Description
「研究成果報告書概要(欧文)」より
