This Special Issue of Prion presents papers based around presentations from PRION 2013 that was held in Banff, Alberta, Canada in May 2013. The conference, hosted by the Alberta Prion Research Institute, was organized into four thematic areas: socioeconomic impacts of prion diseases; protein structure and biology; prion diseases in animals; and, prion and prion-like diseases in humans. Two workshops in the areas of animal and human diseases were held in conjunction with the main conference. This issue has contributions in the predominant themes of the conference. Given the fundamental similarities in prion mechanisms across species, it is not surprising that a number of the papers have application in more than one of the conference themes.
A number of papers have substantial bases in structure, biology and pathobiology of prion and prion-like diseases. The paper by Puig et al. (pp. 11–18) reviews the GPI anchoring of the prion protein and how differences in GRI-anchor composition could modify the prion disease process. Silva (pp. 42–50) discusses the use of mass spectrometry and covalent modification for detection and structural elucidation of prions. Taking a different approach, Requena and Wille (pp. 60–66) review the recent experimental data and models for prion structure, and come to the conclusion that none of the existing models of PrPSc structure fully account for all existing data, suggesting a need for additional structural data to develop a fully reliable structure for future studies. Supattapone (pp. 100–105) describes the potentially important role that cofactors have in maintaining the infectious form of prions. In describing how proteolytic fragments of PrPC might be useful inhibitors of prion propagation Béland and Roucou (pp. 106–110) provide insights on the involvement of structure in pathobiology and therapy. Kabir and Safar (pp. 111–116) provide a stimulating analysis of potential strain evolution and its role in human diseases. And Cheng and Daggett (pp. 125–135) have used molecular dynamics simulations to characterize folding pathways and intermediates in some human mutants to elucidate common intermediates and unique conformers which might lead to strain differences.
Some papers could be considered to have a primary focus on animal prion diseases, and their pathogenesis and prevention. The contribution by Taschuk et al. (pp. 51–59) deals with the development of a vaccine against an epitope exposed on PrPSc (but not on PrPC) which is targeted to chronic wasting disease in cervids. Nokihara et al. (pp. 117–118) describe designed and naturally-occurring brain peptides which accelerate structural conversions in recombinant bovine prion protein. The work described by Majer and Booth (pp. 67–74) on microdissection and transcriptional profiling provides a useful approach to understanding and measuring preclinical prion diseases in animals and humans. A dual impact on animal and human prion diseases is found in the paper of Harischandria et al. (pp. 143–153) on oxidative stress and activation of protein kinase Cð. Rasmussen at al. (pp. 136–142) study the potential for wheat to be a vector for chronic wasting disease prions.
A number of papers mentioned above have impact for human prion diseases, also. The papers by Puig et al., Requena and Wille, Majer and Booth, Supattapone, Béland and Roucou, Kabir and Safir, Cheng and Daggett, and Harischandra et al. would fall into this group. The analysis of the zoonotic potential of animal prion diseases by Barria et al. (pp. 85–91) explores some of the fundamental links between animal and human diseases.
In addition, there is a provocative proposal by Nyström and Hammerström (pp. 2–10) on the origins of the prevalence of the human 29M/V mutation.
A group of papers addresses similarities between prion diseases and those other human diseases that have prion-like properties. Kabir and Safir speculate on the possibilities that the phenotypical traits of other protein misfolding neurological diseases might arise from a spectrum of misfolded conformers like prion strains. Narkiewicz et al. (pp. 19–32) describe means to assess the prion-like properties of 〈-synuclein. Grad and Cashman (pp. 33–41) report on the prion-like activity of Cu/Zn superoxide dismutase and its implications for amyotrophic lateral sclerosis. The contribution by Kumar and Sim (pp. 119–124) looks at the therapeutic potential of D-amino acids peptides in Alzheimer disease. Moving beyond neurodegenerative disease, Rangel et al. (pp. 75–84) explore aggregation of mutant p53 and the prion-like properties of cancer cells.
PRION 2013 was a venue for many exceptionally interesting new perspectives on prion and prion-like diseases. We hope that you find the papers in this volume informative and stimulating in the spirit of those presented at the conference.