Transmissible Spongiform Encephalopathies

Abstract

Prion disease is a unique category of illness, affecting both animals and humans, in which the underlying pathogenesis is related to a conformational change of a normal, self-protein called PrP^C (C for cellular) to a pathological and infectious conformer known as PrP^Sc (Sc for scrapie) (Prusiner, Annu Rev Genet 47:601–623, 2013; Aguzzi and Falsig, Nat Neurosci 15:936–939, 2012; Kretzschmar and Tatzelt, Brain Pathol 23:321–332, 2013; Greenlee and Greenlee, ILAR J 56:7–25, 2015). Currently all prion diseases are without effective treatment and are universally fatal (Prusiner, Annu Rev Genet 47:601–623, 2013; Aguzzi and Falsig, Nat Neurosci 15:936–939, 2012; Greenlee and Greenlee, ILAR J 56:7–25, 2015; Colby and Prusiner, Cold Spring Harb Perspect Biol 3:a006833, 2011; Wisniewski and Goni, Expert Rev Anti Infect Ther 10:307–317, 2012; Sim, Infect Disord Drug Targets 12:144–160, 2012; Rubenstein et al., Prion diagnosis. Manual of clinical and laboratory immunology, 2015). It is increasingly being recognized that many neurodegenerative diseases, such as Alzheimer’s disease (AD), have similarities in their pathogenesis and are “prion-like” (Goedert, Science 349:1255555, 2015; Jucker and Walker, Ann Neurol 70:532–540, 2011; Aguzzi and O’Connor, Nat Rev Drug Discov 9:237–248, 2010; Marciniuk et al., Clin Dev Immunol 2013:473706, 2013). Hence, any effective therapeutic intervention for prion disease would have significant implications for many other common neurodegenerative diseases. Interest in prion disease greatly increased during the emergence of bovine spongiform encephalopathy (BSE) and the resulting appearance of variant CJD (vCJD) in human populations. BSE arose from the feeding of cattle with prion-contaminated meat and bone meal products, while vCJD developed following the entry of BSE into the human food chain (Greenlee and Greenlee, ILAR J 56:7–25, 2015; Harman and Silva, J Am Vet Med Assoc 234:59–72, 2009; Sikorska et al., Adv Exp Med Biol 724:76–90, 2012). A more recently emerging prionoses is chronic wasting disease (CWD), which infects large numbers of cervids in North America, with the potential to infect other agriculturally important species and domestic animals, as well as humans (Rubenstein et al., Prion diagnosis. Manual of clinical and laboratory immunology, 2015; Saunders et al., Emerg Infect Dis 18:369–376, 2012; Gilch et al., Top Curr Chem 305:51–77, 2011; Daus and Beekes, Prion 6:17–22, 2012; Mathiason et al., J Virol 87:1947–1956, 2013). CWD is the most efficiently transmissible naturally occurring prion disease, including by aerosol transmission (Denkers et al., J Virol 87:1890–1892, 2013). In this chapter we review current knowledge regarding TSE and potential therapeutic approaches that are under development.