title: Modulation of amyloid-β aggregation by histidine-coordinating Cobalt(III) Schiff base complexes.
abstract: Oligomers of the Aβ42 peptide are significant neurotoxins linked to Alzheimer's disease (AD). Histidine (His) residues present at the N terminus of Aβ42 are believed to influence toxicity by either serving as metal-ion binding sites (which promote oligomerization and oxidative damage) or facilitating synaptic binding. Transition metal complexes that bind to these residues and modulate Aβ toxicity have emerged as therapeutic candidates. Cobalt(III) Schiff base complexes (Co-sb) were evaluated for their ability to interact with Aβ peptides. HPLC-MS, NMR, fluorescence, and DFT studies demonstrated that Co-sb complexes could interact with the His residues in a truncated Aβ16 peptide representing the Aβ42 N terminus. Coordination of Co-sb complexes altered the structure of Aβ42 peptides and promoted the formation of large soluble oligomers. Interestingly, this structural perturbation of Aβ correlated to reduced synaptic binding to hippocampal neurons. These results demonstrate the promise of Co-sb complexes in anti-AD therapeutic approaches.
authors: Departments of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113 (USA).
authors: Marie C
authors: MC
authors: Heffern
authors: Pauline T
authors: PT
authors: Velasco
authors: Lauren M
authors: LM
authors: Matosziuk
authors: Joseph L
authors: JL
authors: Coomes
authors: Constantine
authors: C
authors: Karras
authors: Mark A
authors: MA
authors: Ratner
authors: William L
authors: WL
authors: Klein
authors: Amanda L
authors: AL
authors: Eckermann
authors: Thomas J
authors: TJ
authors: Meade
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D009942:Organometallic Compounds; D012545:Schiff Bases; D003035:Cobalt; D006639:Histidine
keywords: Alzheimer's disease; amyloid beta; cobalt; histidine; oligomers