Article

Prion strain discrimination using luminescent conjugated polymers.

UniversitätsSpital Zürich, Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Nature Methods (Impact Factor: 25.95). 01/2008; 4(12):1023-30. DOI: 10.1038/nmeth1131
Source: PubMed

ABSTRACT The occurrence of multiple strains of prions may reflect conformational variability of PrP(Sc), a disease-associated, aggregated variant of the cellular prion protein, PrP(C). Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences resulted from distinct supramolecular PrP structures. LCPs may help to detect structural differences among discrete protein aggregates and to link protein conformational features with disease phenotypes.

3 Followers
 · 
137 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biocompatible or biodegradable hyperbranched polymers (HBPs), an important subclass of hyperbranched macromolecules, have recently received an increasing attention due to their unique physical and chemical properties as well as their great advantages in therapeutic applications. This review highlights recent advances and future trends in the preparation and applications of biocompatible or biodegradable HBPs for therapeutic purpose. Various biocompatible or biodegradable hyperbranched structures can be obtained by means of step-growth polycondensation (SGP), self-condensing vinyl polymerization (SCVP), self-condensing ring-opening polymerization (SCROP), and so forth. The properties of biocompatible or biodegradable HBPs can be tailored for a specialized purpose through terminal modification, backbone modification, or hybrid modification. A particular emphasis is then placed on their diagnostic, therapeutic delivery and theranostic applications. Finally, future directions and perspectives in this emerging field are briefly discussed. These developments on synthesis and therapeutic applications of biocompatible or biodegradable HBPs promote the interdisciplinary research spanning polymer materials and biomedical sciences.
    02/2015; 6(15). DOI:10.1039/C5PY00144G
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronicwasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrPSc) in the central nervous system and other tissues, depending on the host pecies. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 05/2015; 56(1):7-25. DOI:10.1093/ilar/ilv008 · 1.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A naturally occurring transmissible spongiform encephalopathy (TSE) of mule deer was first reported in Colorado and Wyoming in 1967 and has since spread to other members of the cervid family in 22 states, 2 Canadian provinces, and the Republic of Korea. Chronic wasting disease (CWD), caused by exposure to an abnormally folded isoform of the cellular prion protein, is characterized by progressive neurological disease in susceptible natural and experimental hosts and is ultimately fatal.CWDis thought to be transmitted horizontally in excreta and through contaminated environments, features common to scrapie of sheep, though rare among TSEs. Evolving detection methods have revealed multiple strains of CWD and with continued development may lead to an effective antemortem test. Managing the spread of CWD, through the development of a vaccine or environmental cleanup strategies, is an active area of interest. As such, CWD represents a unique challenge in the study of prion diseases. Expected final online publication date for the Annual Review of Animal Biosciences Volume 3 is February 15, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    10/2014; 3(1). DOI:10.1146/annurev-animal-022114-111001