Potential candidate camelid antibodies for the treatment of protein-misfolding diseases.

Abstract

Protein-misfolding diseases (PMDs), including Alzheimer's disease would potentially reach epidemic proportion if effective ways to diagnose and treat them were not developed. The quest for effective therapy for PMDs has been ongoing for decades and some of the technologies developed so far show great promise. We report here the development of antibodies by immunization of camelids with prion (PrioV3) and Alzheimer's (PrioAD12, 13 & 120) disease-derived brain material. We show that anti-PrP antibody transmigration across the blood-brain barrier (BBB) was inhibited with phosphatidylinositol-specific phospholipase C (PIPLC). Our camelid anti-prion antibody was also shown to permanently abrogate prion replication in a prion-permissive cell line after crossing the artificial BBB. Furthermore, anti-Aβ/tau antibodies were able to bind their specific immunogens with ELISA and immunohistochemistry. Finally, both PrioV3 and PrioAD12 were shown to co-localize with Lamp-1, a marker of late endosomal/lysosomal compartments. These antibodies could prove to be a valuable tool for the neutralization/clearance of PrP(Sc), Aβ and tau proteins in cellular compartments of affected neurons and could potentially have wider applicability for the treatment of PMDs.

• Authors: Monique Antoinette David, Daryl Rhys Jones, Mourad Tayebi
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 272 Issue 1-2 Pg. 76-85 (Jul 15 2014) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 24864011 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antibodies
• Antigens, CD
• CD71 antigen
• Clathrin
• Peptides
• PrPSc Proteins
• Receptors, Transferrin
• tau Proteins

Topics

• Amyloid beta-Peptides (immunology, metabolism)
• Animals
• Antibodies (therapeutic use)
• Antigens, CD (metabolism)
• Blood-Brain Barrier (pathology)
• Brain (metabolism, pathology)
• Camelus
• Cell Line, Tumor
• Clathrin (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• In Vitro Techniques
• Mice
• Neurotoxicity Syndromes (etiology, metabolism)
• Peptides (metabolism)
• PrPSc Proteins (immunology, metabolism)
• Proteostasis Deficiencies (therapy)
• Receptors, Transferrin (metabolism)
• Time Factors
• tau Proteins (immunology, metabolism)