Epitope specific anti-prion antibodies up-regulate apolipoprotein e and disrupt membrane cholesterol homeostasis.
Summary of "Epitope specific anti-prion antibodies up-regulate apolipoprotein e and disrupt membrane cholesterol homeostasis."
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 over-expression of apolipoprotein E (apoE), and to cytoplasmic phospholipase A2 (cPLA(2)) activation as well as to production of prostaglandin (PGE(2)).These results confirm the in vivo toxic effects and indicate that anti-prion antibody treatment of neurons lead deleterious effects. Finally, great caution should be exerted when adopting antibody-based therapy for prion diseases.
Affiliation
The Royal Veterinary College;
Journal Details
This article was published in the following journal.
Name: The Journal of general virology
ISSN: 1465-2099
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20797970
- DOI: http://dx.doi.org/10.1099/vir.0.023838-0
Medical and Biotech [MESH] Definitions
Epitope Mapping
Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.
Prpsc Proteins
Abnormal isoform of prion proteins (PRIONS) resulting from a posttranslational modification of the cellular prion protein (PRPC PROTEINS). PrPSc are disease-specific proteins seen in certain human and animal neurodegenerative diseases (PRION DISEASES).
Antibodies, Anti-idiotypic
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Beta 2-glycoprotein I
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
Apolipoprotein E4
A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.
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