Transmission of circulating cell-free AA amyloid oligomers in exosomes vectors via a prion-like mechanism.

Abstract

Recent studies clearly demonstrated that several types of pathogenic amyloid proteins acted as agents that could transmit amyloidosis by means of a prion-like mechanism. Systemic AA amyloidosis is one of the most severe complications of chronic inflammatory disorders, particularly rheumatoid arthritis. It is well known that, similar to an infectious prion protein, amyloid-enhancing factor (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits AA amyloidosis in vivo remained to be fully elucidated. In the present study, we focused on finding cell-free forms of AEF and its carriers in circulation by using the murine transfer model of AA amyloidosis. We first determined that circulating cell-free AEF existed in blood and plasma in mice with systemic AA amyloidosis. Second, we established that plasma exosomes containing AA amyloid oligomers derived from serum amyloid A had AEF activity and could transmit systemic AA amyloidosis via a prion-like mechanism. These novel findings should provide insights into the transmission mechanism of systemic amyloidoses.

• Authors: Masayoshi Tasaki, Mitsuharu Ueda, Sho Ochiai, Yuko Tanabe, Sho Murata, Yohei Misumi, Yu Su, Xuguo Sun, Satoru Shinriki, Hirofumi Jono, Makoto Shono, Konen Obayashi, Yukio Ando
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 400 Issue 4 Pg. 559-62 (Oct 01 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20807507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Glycoproteins
• Prions
• Serum Amyloid A Protein
• amyloid enhancing factor

Topics

• Amyloidosis (blood, metabolism)
• Animals
• Exosomes (metabolism)
• Glycoproteins (blood, metabolism)
• Male
• Mice
• Mice, Inbred C3H
• Prions (metabolism)
• Serum Amyloid A Protein (metabolism)