Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases characterized by neuron loss, glial reactions, and tissue spongiosis, which course with motor and/or cognitive symptoms. The TSEs are associated with conformational conversion of the prion protein (PrPC, the product of the Prnp gene), wherein the predominantly α-helical secondary structure of PrPC changes into an aggregation-prone, β-sheet-rich structure known as PrPSc. The latter is believed to coerce PrPC molecules into conformational conversion, thus behaving as a proteinaceous infectious particle, or prion, which gave TSEs the epithet prion diseases (Colby and Prusiner 2011).
The much needed development of effective treatment for these still incurable diseases depends on the understanding of functional properties of the prion protein. Most studies of physiological functions of PrPChave been...
The authors’ research groups have been supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Programa Institutos Nacionais de Ciência e Tecnologia (CNPq/MCT), Canadian Institutes of Health Research (CIHR), the Weston Brain Institute, Brain Canada, The Alzheimer’s Association (USA), The Alzheimer’s Society (Canada), and PrioNet-Canada. V.R.M. is an International Scholar of the Howard Hughes Medical Institute.