'Nature-inspired' drug-protein complexes as inhibitors of Abeta aggregation

Biochem Soc Trans. 2005 Aug;33(Pt 4):543-7. doi: 10.1042/BST0330543.


Protein-protein interactions are a regulatory mechanism for a number of physiological and pathological cellular processes. Neurodegenerative diseases, such as AD (Alzheimer's disease), are associated with the accelerated production or delayed clearance of protein aggregates. Hence, inhibition of pathologic protein-protein interactions is a very attractive mechanism for drug development. This review focuses on a novel therapeutic strategy to inhibit the de novo formation of protein aggregates. Inspired by strategies used in Nature and optimized over millions of years of evolution, we have created a bifunctional molecule [SLF (synthetic ligand for FK506-binding protein)-CR (Congo Red)] that is able to block Abeta (amyloid beta) aggregation by borrowing the surface and steric bulk of a cellular chaperone.

Publication types

  • Review

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Congo Red / pharmacology
  • Humans
  • Multiprotein Complexes / drug effects
  • Multiprotein Complexes / metabolism
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism*
  • Tacrolimus Binding Proteins / metabolism


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Multiprotein Complexes
  • Congo Red
  • Tacrolimus Binding Proteins