Structural and Functional Insights into the Selective Inhibition of Mutant Tau Aggregation by Purpurin and Oleocanthal in Frontotemporal Dementia

Zenodo Dataset Description This dataset provides source data and supplementary materials for the manuscript entitled"Structural and Functional Insights into the Selective Inhibition of Mutant Tau Aggregation by Purpurin and Oleocanthal in Frontotemporal Dementia." Each file corresponds to specific figures in the main text or supplementary material to enable transparent data access and reproducibility. Source Data Files Source Data File 1 (Figure 1b):Raw Thioflavin T fluorescence data for the aggregation kinetics of tau peptides (WT, P301L, V287I, and N279K) shown in Figure 1b. Source Data File 2 (Figure 2a–b):Raw sensorgram data from surface plasmon resonance titration curve kinetics of purpurin and oleocanthal binding with WT and mutant R2R3 tau peptides, shown in Figure 2a and 2b. Source Data File 3 (Figure 3a–d):Raw Thioflavin T fluorescence data showing dose-dependent aggregation inhibition of WT and mutant tau peptides by purpurin and oleocanthal, corresponding to Figure 3a–d. Source Data File 4 (Figure 4a):Thioflavin T fluorescence traces depicting the elongation of preformed WT and P301L tau fibrils before and after treatment with purpurin or oleocanthal, shown in Figure 4a. Source Data File 5 (Figure 5b):Quantification of CFP/YFP-positive inclusions and total cell count used to calculate normalized aggregate numbers in Tau RD P301S biosensor cells, shown in Figure 5b. Source Data File 6 (Figure 6c):Quantification of intracellular aggregates (CFP/YFP inclusions) and cell count following post-transduction treatment with purpurin or oleocanthal, shown in Figure 6c. Supplementary Data Files Source Data File S1 (Figure S4):Fluorescence measurements of ThT, purpurin, and oleocanthal in the absence of peptide, shown in Supplementary Figure S4. Source Data File S2 (Figure S13a):ThT fluorescence data for elongation inhibition of V287I and N279K tau peptides, before and after treatment with purpurin or oleocanthal, shown in Supplementary Figure S13a. Source Data File S3 (Figure S16):Raw MTS absorbance values used to determine IC₅₀ values for purpurin and oleocanthal in Tau biosensor and CCRF-CEM cells, shown in Supplementary Figure S16. Supplementary Dataset S1:MM-GBSA binding free energy calculations for purpurin and oleocanthal bound to WT and P301L tau filaments. Supplementary Dataset S2:Residue-level decomposition analysis of purpurin and oleocanthal interactions with WT and P301L tau filaments. Computational Methods Document Title: Computational Methods – Monomeric Tau Docking and SimulationThis file provides detailed protocols for AlphaFold2-based structure prediction, molecular docking, MM-GBSA energy calculations, and molecular dynamics simulations of monomeric WT and P301L tau peptides with purpurin and oleocanthal. These methods support Supplementary Figures S9–S10 and Tables S1–S2 in the manuscript.