Inhibitory effect of epigallocatechin-3-gallate as a potent anti-amyloidogenic agent against the G138E mutant of SOD1

SOD1 misfolding leads to protein aggregation, which is a common feature of neurodegenerative diseases such as ALS. The effect of epigallocatechin gallate (EGCG) as a potent anti-amyloidogenic polyphenol on the G138E-SOD1 mutant was investigated using computational/experimental approaches. MD simulation results (RMSD, RMSF, Rg, SASA, PCA, and FEL) showed that EGCG binding stabilizes the mutant in a structure closer to the native structure, which was consistent with the FTIR and DSSP results. Intrinsic fluorescence spectroscopy calculated Ksv and Kq values as 1.8 × 104 M−1 and 5.8 × 1012 M−1s−1, respectively, indicating the participation of a static quenching mechanism. TEM images provide compelling evidence for the potential inhibitory effect of EGCG on protein aggregates in the G138E mutant, confirming the results of the ThT assay. DLS results showed a reduction in the size of aggregated particles in the presence of 80 μM EGCG, confirming the inhibition of amyloid aggregation by this compound. Finally, MTT assay on SH-SY5Y cells showed that cell survival in the presence of SOD1-G138E aggregates was approximately 40%, which increased to 60% with the addition of 80 μM EGCG. Taken together, this study suggests that EGCG may inhibit amyloid aggregation and reduce cytotoxicity by affecting nucleation and structural stabilization, making it a promising compound for ALS therapeutic strategies.