No. 21/May 30, 2008
Green Tea Prevents Deathly Plaque Formation in Parkinson’s and Alzheimer`s – First Results in the Test Tube and with Cell Models
E m b a r g o e d until: Friday, May 30, 2008, 18:00 London Time, 13:00 US Eastern Time
The substance EGCG (Epigallocatechin-3-gallate) from green tea can redirect the deadly process which leads to the accumulation of protein aggregates in Parkinson`s and Alzheimer`s disease. EGCG modulates a cascade of protein misfolding in such a way that the formation of deadly plaques is interrupted, and harmless protein structures emerge instead. Researchers of the Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch, a national research laboratory of the Helmholtz Association in Germany have made this discovery in the test tube and in cell models. The research of Dr. Dagmar Ehrnhoefer and Dr. Jan Bieschke of Professor Erich Wanker`s laboratory in Berlin-Buch has now been published in the journal Nature Structural and Molecular Biology*(http://dx.doi.org/10.1038/nsmb.1437).
EGCG binds directly to unfolded proteins at a very early stage and thus prevents their conversion into toxic aggregates. Instead non-toxic, unstructured round aggregates of a new type are formed, presumably by an alternative folding cascade. “These new aggregates are harmless”, Dr. Bieschke is convinced. He said they took an antibody which recognizes toxic aggregates. However, this antibody is unable to bind to the newly formed protein aggregates that occur after EGCG treatment.
Now the MDC-researchers want to know exactly how EGCG interferes with the “bad” proteins. They collaborate with researchers from the neighbouring Leibniz Institute for Molecular Pharmacology (FMP) using NMR-spectroscopy to identify the structure of the new type of aggregate.
The misfolding of proteins is a complex, multi-step process which eventually leads to the accumulation of dangerous insoluble aggregates. These aggregates are toxic for nerve cells and cause their death. They are associated with a number of disorders, including Parkinson`s and Alzheimer`s, and also Huntington’s disease.
EGCG binds to several proteins that are causative for various protein misfolding disorders. Therefore, the MDC researchers consider EGCG or similar substances to be suitable for the development of drugs to treat neurodegenerative diseases and other amyloid diseases, connected to the formation of toxic plaques. Only in 2006, Dagmar Ehrnhoefer was able to show in Drosophila flies transgenic for Huntington’s disease, that EGCG reduces the toxicity of deadly plaques.
*Redirecting aggregation pathways: small molecule-mediated conversion of amyloidogenic polypeptides into unstructured, off-pathway oligomers
Dagmar E. Ehrnhoefer1#, Jan Bieschke1#, Annett Boeddrich1, Martin Herbst1, Laura Masino2, Rudi Lurz3, Sabine Engemann1, Annalisa Pastore2, Erich E. Wanker1*
1)
2) National Institute for Medical Research (NIMR), The Ridgeway, Mill
Hill,
3) Max-Planck-Institute for Molecular Genetics, Ihnestrasse 73, 14195
#These authors contributed equally to the wor
Barbara Bachtler
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