title: Prion processing: a double-edged sword?
abstract: The events leading to the degradation of the endogenous PrP(C) (normal cellular prion protein) have been the subject of numerous studies. Two cleavage processes, α-cleavage and β-cleavage, are responsible for the main C- and N-terminal fragments produced from PrP(C). Both cleavage processes occur within the N-terminus of PrP(C), a region that is significant in terms of function. α-Cleavage, an enzymatic event that occurs at amino acid residues 110 and 111 on PrP(C), interferes with the conversion of PrP(C) into the prion disease-associated isoform, PrP(Sc) (abnormal disease-specific conformation of prion protein). This processing is seen as a positive event in terms of disease development. The study of β-cleavage has taken some surprising turns. β-Cleavage is brought about by ROS (reactive oxygen species). The C-terminal fragment produced, C2, may provide the seed for the abnormal conversion process, as it resembles in size the fragments isolated from prion-infected brains. There is, however, strong evidence that β-cleavage provides an essential process to reduce oxidative stress. β-Cleavage may act as a double-edged sword. By β-cleavage, PrP(C) may try to balance the ROS levels produced during prion infection, but the C2 produced may provide a PrP(Sc) seed that maintains the prion conversion process.
authors: UCD School of Biomolecular and Biomedical Science, Conway Institute for Biomolecular and Biomedical Research University College Dublin, Belfield, Dublin 4, Ireland. hilary.mcmahon@ucd.ie
authors: Hilary E M
authors: HE
authors: McMahon
mesh_terms: D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D006801:Humans; D011115:Polyneuropathies / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D011328:Prions; D017382:Reactive Oxygen Species