The infectious agent of transmissible spongiform encephalopathies (TSE) has been considered to be PrPSC, a structural isoform of cellular prion protein PrPC. PrPSC can exist as oligomers and/or as amyloid polymers. Nucleic acids induce structural conversion of recombinant prion protein PrP and PrPC to PrPSC form in solution and in vitro. Here, we report that nucleic acids, by interacting with PrP in solution, produce amyloid fibril and fibres of different morphologies, similar to those identified in the diseased brains. In addition, the same interaction produces polymer lattices and spherical amyloids of different dimensions (15-150 nm in diameters). The polymer lattices show apparent morphological similarity to the two-dimensional amyloid crystals obtained from linear amyloids isolated in vivo. The spherical amyloids structurally resemble "spherical particles" observed in natural spongiform encephalopathy (SE) and in scrapie-infected brains (TSE). We suggest that spherical amyloids, PrPSC-amylospheroids, are probable constituents of the coat of the spherical particles found in vivo and the latter can act as protective coats of the SE and TSE agents in vivo. (C) 2004 Elsevier Ltd. All rights reserved.
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Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, EnglandUniv London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
Wadsworth, JDF
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Jackson, GS
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机构:Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
Jackson, GS
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Hill, AF
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机构:Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
Hill, AF
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Collinge, J
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机构:Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Wille, H
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Michelitsch, MD
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机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Michelitsch, MD
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Guénebaut, V
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机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Guénebaut, V
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Supattapone, S
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机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Supattapone, S
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Serban, A
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机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Serban, A
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Cohen, FE
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机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Cohen, FE
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Agard, DA
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机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Agard, DA
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Prusiner, SB
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Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USAUniv Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
机构:
Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, EnglandUniv London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
Wadsworth, JDF
;
Jackson, GS
论文数: 0引用数: 0
h-index: 0
机构:Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
Jackson, GS
;
Hill, AF
论文数: 0引用数: 0
h-index: 0
机构:Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
Hill, AF
;
Collinge, J
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h-index: 0
机构:Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Prion Unit, London W2 1PG, England
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Wille, H
;
Michelitsch, MD
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Michelitsch, MD
;
Guénebaut, V
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Guénebaut, V
;
Supattapone, S
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Supattapone, S
;
Serban, A
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Serban, A
;
Cohen, FE
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Cohen, FE
;
Agard, DA
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA
Agard, DA
;
Prusiner, SB
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h-index: 0
机构:
Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USAUniv Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA