fig4

Figure 4. Disaggregating binder and PQC enhancer for protein amyloid aggregates. (A) Cryo-EM structure depicting the complex of EGCG with AD-tau PHF. EGCG assumes a primarily planar conformation, with stabilization facilitated by π-π interactions of stacked aromatic rings, reproduced from Seidler et al.^[46]; (B) Solvation energy difference maps illustrating the comparison between tau PHF structures in the absence and presence of EGCG. Red residues indicate increased stability, while blue residues indicate decreased stability. A notable increase in the free energy of Lys340 at the EGCG binding site is observed, reproduced from Seidler et al.^[46]. (C) The stacking of EGCG molecules at an approximate distance of 4.8 Å enables each EGCG molecule to establish hydrogen bonds with specific stacked tau molecules. The curvature of the EGCG stack leads to an expanded spacing on the fibril-facing surface. Figure reproduced from Seidler et al.^[46]. (D) Molecular docking of curcumin in complex with a hexamer peptide model representing the Aβ_1-42 fibril. The docking simulations demonstrate the partial dissociation of the outermost peptide, reproduced from Jakubowski et al.^[53]. (E) Crocetin treatment in 5XFAD mice resulted in significantly elevated levels of LC3B (red), reproduced from Wani et al.^[64]. (F) Crocetin treatment resulted in a significant reduction of brain Aβ load in 5XFAD mice. Representative brain sections and corresponding quantification analysis show the total Aβ levels (6E10 antibody, green) and activated astrocytes (GFAP antibody, red), reproduced from Wani et al.^[64]. Cryo-EM: Cryo-electron microscopic; EGCG: epigallocatechin gallate; GFAP: glial fibrillary acidic protein; PQC: protein quality control.