Abstract
Aggregation of alpha-synuclein (A-Syn) and phosphorylated alphasynuclein (pA-Syn) may underlie the pathology of Parkinson disease (PD. They are main components of Lewy bodies and Lewy neurites which are the intraneuronal inclusions characteristic of the disease. We demonstrate that the polyphenol (−)-epi-gallocatechine gallate (EGCG) inhibits their aggregation, which makes it a candidate for therapeutic intervention in PD. Three methods were used: inhibition by EGCG of A-Syn and pA-syn fibril formation in incubates; inhibition of the A-Syn fluorophore asyn-HiLyte488 binding to plated A-Syn in microwells; and inhibition of the A-SynHiLyte488 probe binding to aggregated A-Syn and pA-Syn in post mortem PD tissue. In the incubation system, human A-Syn and pASyn formed fibrils which were blocked by EGCG in a concentrationdependent manner, as shown by an absence of thioflavin S binding and an absence of fibrils by electron microsocopy. In the microplate assay system, the ED50 of EGCG blocking of A-Syn-HiLyte488 binding to plated A-Syn was 250nM. In the PD tissue based assay, A-Syn and pA-Syn aggregates were recognized by incubation with 7nM of A-Syn-HiL yte488. This binding was blocked by 150nM of EGCG. Our data suggest that EGCG is a potent remodeling agent of fibril formation and may therefore be a novel drug for treatment of PD.
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