Format

Send to

Choose Destination
Curr Opin Struct Biol. 2015 Feb;30:50-56. doi: 10.1016/j.sbi.2014.12.004. Epub 2015 Jan 2.

Inhibition of protein aggregation and amyloid formation by small molecules.

Author information

1
Manchester Institute of Biotechnology, Faculty of Life Sciences, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
2
Laboratoire de Biochimie Théorique, UPR 9080 CNRS, Université Paris Diderot, Sorbonne Paris Cité, IBPC, 13 rue Pierre et Marie Curie, 75005 Paris, France; Institut Universitaire de France, IUF, 103 Boulevard Saint-Michel, 75005 Paris, France. Electronic address: philippe.derreumaux@ibpc.fr.

Abstract

For decades, drug after drug has failed to slow the progression of Alzheimer's disease in human trials. How compounds reducing fibril formation in vitro and toxicity in transgenic mice and flies bind to the Aβ toxic oligomers, is unknown. This account reviews recent drugs mainly targeting Aβ, how they were identified and report their successes from in vitro and in vivo experimental studies and their current status in clinical trials. We then focus on recent in vitro and simulation results on how inhibitors interact with Aβ monomers and oligomers, highly desirable knowledge for predicting new efficient drugs. We conclude with a perspective on the future of the inhibition of amyloid formation by small molecules.

PMID:
25559306
DOI:
10.1016/j.sbi.2014.12.004
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center