Oxidized EGCG redirects α-synuclein aggregation through shear-selected interactions

α-Synuclein (αSyn) aggregation is central to Parkinson's disease pathology, and the green-tea polyphenol epigallocatechin gallate (EGCG) has been studied as an inhibit fibril formation. However, EGCG autoxidation and analyses under static, non-fibrillating conditions have obscured whether activity arises from EGCG itself or oxidized species and which interactions persist during αSyn assembly. Here we combine HPLC, LC-MS, TEM and solution NMR to compare unoxidized and oxidized EGCG (oxEGCG), while Rheo-NMR monitors αSyn during shear-promoted assembly. Unoxidized EGCG showed no detectable binding under static, reducing conditions, whereas oxEGCG bound αSyn, inhibited fibrillation and remodeled fibrils. Under shear flow, many oxEGCG-dependent perturbations partially reverted toward free αSyn, whereas interactions near the NAC–C-terminal boundary were preferentially retained, coinciding with formation of oligomers and short, thick fibrils. These findings identify oxidation state and flow as determinants of EGCG action on αSyn and show that Rheo-NMR distinguishes interactions that persist during shear-promoted assembly.