The study investigates the effects of (-)-epi-gallocatechin gallate (EGCG), a polyphenol found in green tea, on the structure and toxicity of α-synuclein and amyloid-β (Aβ) fibrils. EGCG has been previously shown to inhibit α-synuclein and Aβ fibril formation by binding to unfolded polypeptides and promoting the assembly of unstructured oligomers. However, it was unclear whether EGCG could disassemble preformed amyloid fibrils. The research demonstrates that EGCG can convert large, mature α-synuclein and Aβ fibrils into smaller, amorphous protein aggregates that are non-toxic to mammalian cells. Mechanistically, EGCG directly binds to β-sheet-rich aggregates without disassembling them into monomers or small oligomers. This suggests that EGCG is a potent remodeling agent of mature amyloid fibrils. The findings indicate that EGCG may also influence the conformation of other amyloid structures implicated in diseases such as Alzheimer's and Parkinson's. The study provides evidence that EGCG can reduce the toxicity of amyloid aggregates in both in vitro and in vivo models, suggesting its potential as a therapeutic agent for amyloid-related diseases.The study investigates the effects of (-)-epi-gallocatechin gallate (EGCG), a polyphenol found in green tea, on the structure and toxicity of α-synuclein and amyloid-β (Aβ) fibrils. EGCG has been previously shown to inhibit α-synuclein and Aβ fibril formation by binding to unfolded polypeptides and promoting the assembly of unstructured oligomers. However, it was unclear whether EGCG could disassemble preformed amyloid fibrils. The research demonstrates that EGCG can convert large, mature α-synuclein and Aβ fibrils into smaller, amorphous protein aggregates that are non-toxic to mammalian cells. Mechanistically, EGCG directly binds to β-sheet-rich aggregates without disassembling them into monomers or small oligomers. This suggests that EGCG is a potent remodeling agent of mature amyloid fibrils. The findings indicate that EGCG may also influence the conformation of other amyloid structures implicated in diseases such as Alzheimer's and Parkinson's. The study provides evidence that EGCG can reduce the toxicity of amyloid aggregates in both in vitro and in vivo models, suggesting its potential as a therapeutic agent for amyloid-related diseases.