@article{Christou:2026,
author = {Christou, N and Fitikides, N and Yan, X and Vadukul, D and Ying, L and Vilar, Compte R and Aprile, F},
journal = {ChemMedChem},
title = {Cobalt(III) complexes as promoters of amyloid-β fibril destabilization},
year = {2026}
}

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TY  - JOUR
AB  - Alzheimer’s disease is linked to the formation of pathological aggregates of the amyloid-β peptide in the brain. The N-terminus of amyloid-β plays an important role in modulating aggregation through metal- ion binding. It also remains solvent-accessible in both the monomers and the amyloid fibrils. This observation inspired us to synthesize cobalt(III) metal complexes featuring functionalized aromatic ligands, aimed at targeting amyloid-β N-terminus to influence aggregation. Through chemical kinetic analysis, we found that our cobalt(III) complexes modulate both primary and secondary nucleation pathways. Furthermore, total internal reflection fluorescence microscopy demonstrated that the compounds could disrupt preformed amyloid fibrils. Under physiologically relevant oxidative conditions, inhibition of fibril formation was reduced, whereas fibril disassembly remained largely preserved. This indicates that oxidation selectively impairs the aggregation-inhibiting mechanism without substantially affecting fibril disassembly. These findings suggest that inhibition of aggregation depends on interactions with protein species, e.g., monomers and oligomers, whose conformations are likely altered in an oxidative environment, thereby diminishing compound efficacy. In contrast, the structural features of mature fibrils formed under oxidative conditions remain susceptible to compound-induced destabilization. The preserved disaggregation activity of the cobalt(III) complexes under oxidative conditions resembling those associated with late-stage Alzheimer’s disease supports further investigation of their therapeutic potential.
AU  - Christou,N
AU  - Fitikides,N
AU  - Yan,X
AU  - Vadukul,D
AU  - Ying,L
AU  - Vilar,Compte R
AU  - Aprile,F
PY  - 2026///
SN  - 1860-7179
TI  - Cobalt(III) complexes as promoters of amyloid-β fibril destabilization
T2  - ChemMedChem
ER  - 

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