Founded in 2007 and having completed its 5th year by now, Prion is no longer a toddler, and is increasingly conscious of its international role in the promulgation of prion science. In keeping with this notion, this special issue marks an intercontinental prion conference held in the lovely venue of Montreal in May 2011, the outcome of a fruitful collaboration between PrioNet Canada, the European NeuroPrion Association, and the Alberta Prion Research Institute—three centers of excellence in prion diseases. The first such meeting convened outside of Europe, the conference theme was called “The New World”—not only for its location in North America, but for the novel scientific territory it embraced, especially the prion-like propagated misfolding mechanism applied to common neurological, psychiatric and systemic diseases. The application of prion ideas to Alzheimer, Parkinson and amyotrophic lateral sclerosis is now leading to new therapies and biomarker discovery—but also to new concerns about public health. This theme was emphasized by the plenary talk, presented by Stan Prusiner, a founder of prion concept, and focused on the burgeoning neurobehavioral epidemic linked to multiple concussions—including professional athletes—and characterized pathologically by a frontotemporal tauopathy. Claudio Soto, one of the pioneers of the in vitro assays for prion propagation, also presented startling work indicating that the cerebral amyloidosis of Alzheimer disease can be transmitted through blood transfusion, at least in experimental models. Dr Soto also showed that the pancreatic amyloidosis of type II diabetes is transmissible, again in experimental models. It will take a decade or more for the research community to fully understand the potential human health threats posed by these important discoveries, through careful experimentation and well-designed epidemiologic studies. Another highlight of the Montreal meeting was a roundtable retrospective of Soto’s protein misfolding cyclic amplification (PMCA) entitled “Back to the Future,” which captured much of the validation and promise of the technique since it was originally published in Nature in 2001. This scientific roundtable, involving Claudio, Byron Caughey and Jean-Philippe Deslys, was more informative, although perhaps less entertaining, than Paul Brown’s suggestion to the organizers to contract The Village People to sing “PMCA!”
While papers by Prusiner and Soto are published elsewhere, this issue of Prion details many of the other novel discoveries unveiled at the Montreal meeting. Coincidentally, the issue opens with a legacy testament by one of the Prion 2011 speakers and one of long-time leaders in the prion field, Dr Charles Weissmann called “The End of the Road”—a somewhat sobering title which details with characteristic insight and humor a remarkable career, abstracted as “After some 60 years in research, a few months before my final retirement (there were a few temporary ones), the time has come to reminisce.” As noticed by one of the reviewers of this paper, it is very striking that Dr Weissmann’s most recent research, published in his 2010 Science paper and continued by the results presented at the Prion 2011 meeting, harkens back to the quasispecies concept which occupied so much of his early career. In a conversation with one of the editors of this issue, Dr Weissmann recalled Pasteur’s observation, “chance favors the prepared mind,” and suggested that maybe his mind was prepared by his earlier research to interpret the results on the prion work.
A second special article is provided by Florence Kranitz on The Creutzfeldt-Jakob Disease Foundation. Florence, together with Suzanne Solvyns, delivered a heartbreaking presentation from the CJD International Support Alliance at Prion 2011 meeting, literally turning people to tears. The article presented in the journal is of more “historical” nature, which certainly serves the occasion. Those of us who have been greatly moved by Florence’s humanity and articulation sincerely hope that this article provides a starting point for subsequent publications, which will further expand awareness of the Foundation activities among the prion scientists, and also capture her unique powers.
Seven other review papers on meeting-related materials are included in the issue. Jiri G. Safar provides a masterful minireview highlighting the unsolved mysteries of the molecular pathogenesis of sporadic prion diseases in man. The Claudia Madampage et al. review, from the lab of Jeremy S. Lee, presents data on the application of the new emerging technique, nanopore analysis, in studying conformations of the amyloidogenic proteins, such as Aβ peptides, α-synuclein and prion protein. A review by Gwennaelle J. Wathne and Neil Mabbott highlights the involvement of mononuclear phagocytes in TSE diseases, discussing various possible roles of these cells, from prion trafficking and destruction to modulation of neuropathology. A landmark review by Carsten Korth brings the prion hypothesis to schizophrenia and other chronic mental diseases, mediated by the misfolding and misbehavior of DISC1—a protein product of a gene disrupted in familial schizophrenia—and its binding partner dysbindin. A review by Marilene H. Lopes and Tiago G. Santos, which has provided a beautiful image for the cover of this issue, reveals the role of PrPC in modulation of self-renewal and proliferation in neural stem cells, through stress inducible protein 1 (STI1). A review by Byron Caughey’s group (Christina D. Orru et al.) presents an update on QuIC, a technology that finally seems poised to be an efficient assay for prion infection as applied to accessible biofluids, such as CSF and even blood. A review by Stacie Robinson et al. summarizes data on sequence polymorphisms within the prion protein gene among North American cervids, and on possible links between these polymorphisms and susceptibility to (or progression of) chronic wasting disease.
In addition to reviews, this issue of Prion also includes three research papers, describing and/or further expanding some results presented at the Prion 2011 meeting. Christopher Silva provides an important research article expanding the utility of “epitope protection” to determine the aggregation and even conformational state of misfolded prion proteins, including a rational methodology to map epitopes exposed during misfolding in disease. A paper by Silvia Siso et al. addresses an important issue of prion stability across the species barrier by re-infecting sheep with the sheep-derived scrapie strains propagated in mice and demonstrating that these strains produce distinct but variable disease patterns in sheep, following adaptation in a new host. An important research paper comes from the Eliezer Masliah and Christina J. Sigurdson groups. This work shows that experimental infection with prions triggers the aggregation and accumulation of α-synuclein in aged transgenic mice expressing human α-synuclein.
We hope that this sample of excellent research presented at Prion 2011 will provide readers with up-to-date glance at various developments in the prion field.