title: Epitope-specific anti-prion antibodies upregulate apolipoprotein E and disrupt membrane cholesterol homeostasis.
abstract: The mechanisms of neuronal degeneration induced by the transformation of normal cellular prion protein (PrP(C)) into disease-associated PrP(Sc) are not fully understood. Previous reports have demonstrated that cross-linking cellular prion protein by anti-PrP(C) antibodies can promote neuronal apoptosis. In this report, we now show that treatment of neuronal cells with anti-prion antibodies leads to sequestration of free cholesterol in cell membranes, significant overexpression of apolipoprotein E, and to cytoplasmic phospholipase A2 activation as well as to production of prostaglandin. These results confirm the in vivo toxic effects and indicate that anti-prion antibody treatment of neurons lead to deleterious effects. Finally, great caution should be exerted when adopting antibody-based therapy for prion diseases.
authors.affiliation: Brain & Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia.
authors.forename: Mourad
authors.initials: M
authors.lastname: Tayebi
authors.forename: Monique
authors.initials: M
authors.lastname: David
authors.forename: Clive
authors.initials: C
authors.lastname: Bate
authors.forename: Daryl
authors.initials: D
authors.lastname: Jones
authors.forename: William
authors.initials: W
authors.lastname: Taylor
authors.forename: Rebecca
authors.initials: R
authors.lastname: Morton
authors.forename: John
authors.initials: J
authors.lastname: Pollard
authors.forename: Simon
authors.initials: S
authors.lastname: Hawke
mesh_terms: D000906:Antibodies / Q000276:immunology*; D001057:Apolipoproteins E / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D011328:Prions / Q000276:immunology*
chemical_list: D000906:Antibodies; D001057:Apolipoproteins E; D000939:Epitopes; D011328:Prions; D002784:Cholesterol