Oligomeric Amyloid-β Toxicity Can Be Inhibited by Blocking Its Cellular Binding in Cortical Neuronal Cultures with Addition of the Triphenylmethane Dye Brilliant Blue G.
Accumulation of soluble amyloid β (Aβ) oligomers in the brain has been suggested to cause neurodegeneration associated with Alzheimer's disease (AD). Our previous findings showed that the binding of Aβ trimer and tetramer to neurons is significantly correlated with Aβ-induced neuronal cell death. We propose blocking of neuronal binding of these neurotoxic Aβ oligomers as a therapeutic strategy for preventing this disease. To test this, a nontoxic triphenylmethane dye, Brilliant Blue G (BBG), which has been reported to modulate Aβ aggregation and neurotoxicity, was investigated using mouse primary cortical neuronal cultures treated with photoinduced cross-linked toxic Aβ40 oligomers as well as soluble Aβ40 and Aβ42 peptides. We found that the BBG-induced decrease in Aβ binding resulted in a significant decrease in its neurotoxicity. These findings support our hypothesis that disruption of cellular Aβ binding is a promising therapeutic strategy for combating AD.
Department of Pathology, The University of Melbourne , Parkville, VIC 3010, Australia.
Metta K
MK
Jana
Department of Pathology, The University of Melbourne , Parkville, VIC 3010, Australia.
Roberto
R
Cappai
Department of Pathology, The University of Melbourne , Parkville, VIC 3010, Australia.
Giuseppe D
GD
Ciccotosto
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012394:Rosaniline Dyes / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012394:Rosaniline Dyes; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C004692:coomassie Brilliant Blue
Alzheimer’s disease (AD); PICUP; amyloid β (Aβ); brilliant blue G; oligomer; tetramer; toxicity