EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity

Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7710-5. doi: 10.1073/pnas.0910723107. Epub 2010 Apr 12.


Protein misfolding and formation of beta-sheet-rich amyloid fibrils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimer's and Parkinson's disease. Recently, we demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis. It associates with natively unfolded polypeptides and promotes the self-assembly of unstructured oligomers of a new type. Whether EGCG disassembles preformed amyloid fibrils, however, remained unclear. Here, we show that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies revealed that the compound directly binds to beta-sheet-rich aggregates and mediates the conformational change without their disassembly into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / biosynthesis*
  • Amyloid / drug effects
  • Amyloid Neuropathies / drug therapy
  • Amyloid Neuropathies / prevention & control*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blotting, Western
  • CHO Cells
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Chromatography, Affinity
  • Circular Dichroism
  • Cricetinae
  • Cricetulus
  • Escherichia coli
  • Humans
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Rats
  • alpha-Synuclein / metabolism*


  • Amyloid
  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • alpha-Synuclein
  • Catechin
  • epigallocatechin gallate