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. The accumulation of beta-sheet–rich amyloid fibrils or aggregates is a complex, multistep process that is associated with cellular toxicity in a number of human protein misfolding disorders, including Parkinson's and Alzheimer's diseases. It involves the formation of various transient and intransient, on- and off-pathway aggregate species, whose structure, size and cellular toxicity are largely unclear. 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. They demonstrate redirection of amyloid fibril formation through the action of a small molecule, resulting in off-pathway, highly stable oligomers. The polyphenol (- )-epigallocatechin gallate efficiently inhibits the fibrillogenesis of both alpha-synuclein and amyloid-beta by directly binding to the natively unfolded polypeptides and preventing their conversion into toxic, on-pathway aggregation intermediates. Instead of beta-sheet–rich amyloid, the formation of unstructured, nontoxic -synuclein and amyloid-beta oligomers of a new type is promoted, suggesting a generic effect on aggregation pathways in neurodegenerative diseases.
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. ...http://www.medicalnewstoday.com
posted by Valery Yermalitsky at
8:52 AM
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