Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation: A Potential Agent for Parkinson's Disease.

Abstract

Protein aggregation is a prominent feature of many neurodegenerative disorders including Parkinson's disease (PD). Aggregation of alpha-synuclein (SNCA) may underlie the pathology of PD. They are the main components of Lewy bodies and dystrophic neurites that are the intraneuronal inclusions characteristic of the disease. We have demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibited SNCA aggregation, which made it a candidate for therapeutic intervention in PD. Three methods were used: SNCA fibril formation inhibition by EGCG in incubates; inhibition of the SNCA fluorophore A-Syn-HiLyte488 binding to plated SNCA in microwells; and inhibition of the A-Syn-HiLyte488 probe binding to aggregated SNCA in postmortem PD tissue. Recombinant human SNCA was incubated under conditions that result in fibril formation. The aggregation was blocked by 100 nM EGCG in a concentration-dependent manner, as shown by an absence of thioflavin T binding. In the microplate assay system, the ED50 of EGCG inhibition of A-Syn-HiLyte488 binding to coated SNCA was 250 nM. In the PD tissue based assay, SNCA aggregates were recognized by incubation with 7 nM of A-Syn-HiLyte488. This binding was blocked by EGCG in a concentration dependent manner. The SNCA amino acid sites, which potentially interacted with EGCG, were detected on peptide membranes. It was implicated that EGCG binds to SNCA by instable hydrophobic interactions. In this study, we suggested that EGCG could be a potent remodeling agent of SNCA aggregates and a potential disease modifying drug for the treatment of PD and other α-synucleinopathies.

• Authors: Yan Xu, Yanyan Zhang, Zhenzhen Quan, Winnie Wong, Jianping Guo, Rongkai Zhang, Qinghu Yang, Rongji Dai, Patrick L McGeer, Hong Qing
• Journal: Neurochemical research (Neurochem Res) Vol. 41 Issue 10 Pg. 2788-2796 (Oct 2016) ISSN: 1573-6903 [Electronic] United States
• PMID: 27364962 (Publication Type: Journal Article)

Chemical References

• SNCA protein, human
• alpha-Synuclein
• Catechin
• epigallocatechin gallate

Topics

• Catechin (analogs & derivatives, pharmacology)
• Cells, Cultured
• Humans
• Lewy Bodies (drug effects, metabolism)
• Parkinson Disease (drug therapy, metabolism, pathology)
• alpha-Synuclein (metabolism)