Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity

Although fibrillar amyloid beta peptide (A?) aggregates are one of the major hallmarks of Alzheimer's disease, increasing evidence suggests that soluble A? oligomers are the primary toxic species. Targeting the oligomeric species could represent an effective strategy to interfere with A? toxicity. In this work, the biological properties of 5[4-(6-O-?-cyclodextrin)-phenyl],10,15,20-tri(4-hydroxyphenyl)-porphyrin and its zinc complex were tested, as new molecules that interact with A? and effectively prevent its cytotoxicity. We found that these systems can cross the cell membrane to deliver A? intracellularly and promote its clearance. Our results provide evidence for the use of cyclodextrin-porphyrin derivatives as a promising strategy to target amyloid aggregation.