Details

Autor(en) / Beteiligte

• Zhang, Tong
• Zhang, Jian
• Derreumaux, Philippe
• Mu, Yuguang

Titel

Molecular Mechanism of the Inhibition of EGCG on the Alzheimer Aβ1–42 Dimer

Ist Teil von

• The journal of physical chemistry. B, 2013-04, Vol.117 (15), p.3993-4002

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Growing evidence supports that amyloid β (Aβ) oligomers are the major causative agents leading to neural cell death in Alzheimer’s disease. The polyphenol (−)-epigallocatechin gallate (EGCG) was recently reported to inhibit Aβ fibrillization and redirect Aβ aggregation into unstructured, off-pathway oligomers. Given the experimental challenge to characterize the structures of Aβ/EGCG complexes, we performed extensive atomistic replica exchange molecular dynamics simulations of Aβ1–42 dimer in the present and absence of EGCG in explicit solvent. Our equilibrium Aβ dimeric structures free of EGCG are consistent with the collision cross section from ion-mobility mass spectrometry and the secondary structure composition from circular dichroism experiment. In the presence of EGCG, the Aβ structures are characterized by increased inter-center-of-mass distances, reduced interchain and intrachain contacts, reduced β-sheet content, and increased coil and α-helix contents. Analysis of the free energy surfaces reveals that the Aβ dimer with EGCG adopts new conformations, affecting therefore its propensity to adopt fibril-prone states. Overall, this study provides, for the first time, insights on the equilibrium structures of Aβ1–42 dimer in explicit aqueous solution and an atomic picture of the EGCG-mediated conformational change on Aβ dimer.