title: Is loss of function of the prion protein the cause of prion disorders?
abstract: Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that involve misfolding of the prion protein. Recent studies have provided evidence that normal prion protein might have a physiological function in neuroprotective signaling, suggesting that loss of prion protein activity might contribute to the pathogenesis of prion disease. However, studies using knockout animals do not support the loss-of-function hypothesis and argue that prion neurodegeneration might be associated with a gain of a toxic activity by the misfolded prion protein. Thus, the mechanism of neurodegeneration in spongiform encephalopathies remains enigmatic.
authors.affiliation: Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan les Ouates, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
authors.forename: Kinsey
authors.initials: K
authors.lastname: Maundrell
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000818:Animals; D002417:Cattle; D058851:GPI-Linked Proteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009474:Neurons / Q000473:pathology; D017096:Prion Diseases / Q000209:etiology* / Q000473:pathology; D011328:Prions / Q000378:metabolism / Q000502:physiology*; D017510:Protein Folding; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D058851:GPI-Linked Proteins; C501125:PRND protein, human; D011328:Prions; C122036:Prnd protein, mouse; D020033:Protein Isoforms