Is loss of function of the prion protein the cause of prion disorders?
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.
Hetz
Claudio
C
Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan les Ouates, Switzerland.
Maundrell
Kinsey
K
Soto
Claudio
C
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
D058851:GPI-Linked Proteins; C501125:PRND protein, human; D011328:Prions; C122036:Prnd protein, mouse; D020033:Protein Isoforms