Journal
FEBS LETTERS
Volume 589, Issue 7, Pages 849-856Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2015.02.020
Keywords
CHF5074 (CSP-1103); Familial amyloidotic polyneuropathy; Misfolding; Retinol binding protein; Transthyretin
Funding
- Japan Society for the Promotion of Science
- CREST (JST)
- Grants-in-Aid for Scientific Research [24590404, 221S0001] Funding Source: KAKEN
Ask authors/readers for more resources
Familial amyloidotic polyneuropathy is one type of protein misfolding disease. Transthyretin (TTR) tetramer dissociation is the limiting step for amyloid fibril formation. CHF5074 (CSP-1103) stabilizes TTR tetramer in vitro by binding to the T4 binding site. Here, we used three strains of double humanized mice (mTtr(hTTRVal30/hTTRVal30), mTtr(hTTRVal30/hTTRMet30), and mTtr(hTTRMet30/hTTRMet30)) to assess whether CHF5074 stabilizes TTR tetramers in vivo. Treatment of mice with CHF5074 increased serum TTR levels by stabilizing TTR tetramers. Although the binding affinities of CHF5074 and diflunisal with TTRMet30 were similar, CHF5074 bound TTRVal30 more strongly than did diflunisal, suggesting the potent TTR-stabilizing activity of CHF5074. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available