Green Tea And Alzheimer's Disease - EGCG Turn Plague Harmless

by Julian

31 May 2008 - A green tea and Alzheimer's disease conducted by a German team discovered how it makes deadly brain plague harmless.

The substance ECGC (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.

ECGC 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 ECGC interferes with the "bad" proteins. They collaborate with researchers from the neighbouring Leibniz Instititute 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.

ECGC binds to several proteins that are causative for various protein misfolding disorders. Therefore, the MDC researchers consider ECGC 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 ECGC reduces the toxicity of deadly plaques.

What Does This Mean?

This method could be more generally used to get rid of or remove the concentration of misfolded proteins in cells," Wanker said.

"This strategy should be tested with patients. If treated early on, it could prevent the formation of amyloid plaque," he speculated.

Whether this type of treatment could reverse plaques that have already formed in the brain isn't known, Wanker said.

He noted that the study remains basic science, and he was cautious about recommending green tea as a way of preventing Alzheimer's disease.

"I don't want to do a lot of speculating which could point people in the direction that could be harmful," Wanker said. "We have to go step-by-step."

One expert believes the approach could yield real results, however.

"Red wine, yellow curry and green tea have suspected health benefits because of high content of antioxidants," said Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System, and associate director of the Alzheimer's Disease Research Center at UCLA David Geffen School of Medicine. He was not involved in the study.

"This study provides evidence that a compound called EGCG, one of the major polyphenols in green tea, may be useful for diseases like Parkinson's and Alzheimer's, because it can block the formation of the filament-forming protein aggregates implicated in causing disease," Cole said.

This green tea and alzheimer study by 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).

Media Release: Green Tea Prevents Deathly Plaque Formation in Parkinson's and Alzheimer`s - First Results in the Test Tube and with Cell Models.