Self-Perpetuating Structural States in Biology, Disease, and Genetics (2002) / Chapter Skim
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Transmission of prions
Transmission of prions
Pages 2-7
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Flechsig§ Medical Research Council Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1 N 3BG, United Kingdom The "protein only" hypothesis states that the infectious agent causing transmissible spongiform encephalopathies is a conformational isomer of PrP, a host protein predominantly expressed in brain, and is strongly supported by many lines of evidence. Prion diseases are so far unique among conformational diseases in that they are transmissible, not only experimentally but also by natural routes, mainly by ingestion.
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Myeloid dendritic cells are thought to mediate transport within the Iymphoreticular system. From the Iymphoreticular system and likely from other sites, prions proceed along the peripheral nervous system to finally reach the brain, either directly via the vagus nerve or via the spinal cord, under involvement of the sympathetic nervous system.
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Most cases are due to injection of cadaveric human growth hormone or transplantation of aura mater; however, a few incidents associated with cornea transplantation have been reported. Four instances of CJD after neurosurgical intervention have been attributed to surgical instruments that had previously been used on CJD patients (69~; however, causality was proven only in one case.
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(A) Stainless steel wires were exposed to scrapie-infected brain homogenates, washed, and placed on a confluent layer of neuroblastoma cells.
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172403799 exceptional in that they are able to enter their hosts by natural portals and make their way from the gut to the brain, utilizing intermediate tissues for amplification. In the case of microbes and viruses, such sophisticated behavior is attributed to evolutionary processes, that is, genomic mutations and selection of mutants that most readily enter their host and find a suitable niche in which to replicate and/or perpetuate themselves; however, prion protein is encoded by the genome of its host.
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(1996) in Prion Diseases, eds.
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