Chapters authored
Past, Present and Potential Future Prion Disease Treatment Strategies
The prion diseases are rare and invariably fatal neurodegenerative diseases characterized by a unique, protein‐only pathogenesis. Mechanistically, the prion diseases result from the coerced conversion of a protease‐sensitive form of the cellular prion protein (PrPC) into a protease‐resistant infectious form (PrPres). This chapter reviews the past, present, and potentially future prion disease treatment strategies. This chapter begins with an introduction to prion diseases, the misfolding of prion proteins and what is known about this process, and then proceeds to discuss approaches for treatments. Regarding approaches to treat prion diseases, we discuss (1) small molecule inhibitors, (2) antiprion protein antibodies, (3) prion gene disruption, (4) targeting of the unfolded protein response, and (5) heterologous prion proteins. We elaborate on using heterologous prion proteins to treat prion diseases, as this is an area that we are pursuing. The chapter ends with thoughts on the future direction of prion disease treatment strategies and how these strategies might be applicable to other neurodegenerative diseases involving protein misfolding. The increasing awareness of the role of protein misfolding in many neurodegenerative processes makes the development of an effective treatment strategy for prion diseases a high priority.
Part of the book: Prion
Neurobehavioral Testing in Prion Disease Studies
The prion diseases are neurodegenerative diseases characterized by progressive neurocognitive decline and terminal dementia. In this review, we will discuss the role of neurobehavioral testing in mammalian prion disease model systems, including (1) a review of the clinical phenotype of the major prion diseases in natural disease, (2) an evidence-based summary of the benefits and shortcomings of commonly used behavioral assays, and (3) a review of the neurobehavioral testing in rodent prion models. Based upon this review, and in light of the established importance of model systems in studies of prion pathogenesis and the proven role of behavioral testing in nonprion disease neurodegenerative diseases, it is vital that prion researchers consider the clinical consequences of prion infection so as to maximize the impact of their work.
Part of the book: Prion