Caister Academic Press

Future Perspectives in Prion Research

Takashi Onodera, Takuya Nishimura and Katsuaki Sugiura
from: Prions: Current Progress in Advanced Research (Second Edition) (Edited by: Akikazu Sakudo and Takashi Onodera). Caister Academic Press, U.K. (2019) Pages: 125-134.


Classic scrapie control can be obtained nationally without loss of genetic polymorphism from any sheep breeds according to recent results from the Netherlands. No classical scrapie strain thus far has escaped ARR-associated resistance. Ongoing studies show that an atypical scrapie strain is also controlled by ARR-associated resistance. In line with these findings, the breeding programme proved successful in a Dutch flock in 2010. When considering rapid outbreak control, as observed in the Netherlands study, the use of resistant rams seems sufficient and can be recommended as a control strategy in scrapie-affected countries. Protein misfolding cyclic amplification (PMCA) needs to be highly standardized and robust in terms of a consistent and objectively quantifiable PrPres amplification if it is to be used for quantification of the proteinaceous seeding activity of prions. There is a direct quantitative correspondence between the seeding and infectious activities of 263K scrapie prions (measured by RT-QuIC) and bioassay. The methodological, conceptual, and practical results described in the report on 263K scrapie prions should be validated for most human transmissible spongiform encephalopathies (TSE) agents. It seems likely that PrPC participates in the pathogenesis of Alzheimer's disease (AD) by acting as a cellular receptor for oligomeric Aβ aggregates. Ablation of PrPC expression or reducing PrPC levels in the brain could be very important therapeutic strategies for CJD and AD. However, chronic treatment with PrPC-lowering drugs may reveal unexpected consequences in the brain. An extensive understanding of the role of PrPC within the brain, especially in humans, is urgently needed. Canadian scientists have succeeded in transmitting chronic wasting disease (CWD) orally in primates. Specifically, 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer or elk via intracerebral, oral, and skin exposure routes. Challenged intracranially with steel wire, or orally, primates were sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. All animals had variable signs of prion neuropathology in their spinal cords and brains. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia, and/or tremor. In four animals, wasting was observed; two of those had confirmed diabetes. CWD contamination in the environment is increasingly important in public health and wildlife. Although scrapie has been known for decades, it has received relatively little attention as a natural disease of sheep and goats mainly because its economic impact has been relatively small compared to other sheep diseases. The occurrence of bovine spongiform encephalopathy (BSE) provides a new impetus to research into the transmissible spongiform encephalopathies (TSE). Not only is the economic impact of BSE much greater than that of scrapie, but the link with variant Creutzfeldt-Jakob disease (vCJD) in humans also gave rise to serious concerns regarding food safety read more ...
Access full text
Related articles ...