Inhibition of amyloid fibril formation of beta-amyloid peptides via the amphiphilic surfactants.
Beta-amyloid peptide (A beta) is the major proteinacious constituent of senile plaques in Alzheimer's disease and is believed to be responsible for the neurodegeneration process associated with the disease. While the actual size of the aggregated species responsible for A beta neurotoxicity and fibrillogenesis mechanism(s) remain unknown, retardation of A beta aggregation still holds assurance as an effective strategy in reducing A beta-elicited toxicity. The research presented here is aimed at examining the inhibitory effect of two amphiphilic surfactants, di-C6-PC and di-C7-PC, on the in vitro fibrillogenesis process of A beta(1--40) peptides at physiological pH (pH 7.2). Using ThT-induced fluorescence, turbidity, Congo red binding, and circular dichroism spectroscopy studies, our research demonstrated that the inhibition of A beta(1--40) fibril formation was di-C6-PC and di-C7-PC concentration-dependent. The best inhibitory action on fibril formation was observed when A beta was incubated with di-C7-PC at 100 microM over time. We believe that the outcome from this work will aid in the development and/or design of potential inhibitory agents against amyloid formation associated with Alzheimer's and other amyloid diseases.
Wang
Steven S-S
SS
Department of Chemical Engineering, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei 10617, Taiwan. sswang@ntu.edu.tw
Chen
Ya-Ting
YT
Chou
Shang-Wei
SW
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D002942:Circular Dichroism; D003224:Congo Red; D004305:Dose-Response Relationship, Drug; D005453:Fluorescence; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology*
C092445:1,2-dihexanoyl-sn-glycero-3-phosphorylcholine; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; C078592:amyloid beta-protein (1-40); C038470:1,2-heptanoylphosphatidylcholine; D003224:Congo Red