{"doi":"10.1101/2020.05.12.091405","title":"Cobalt(III) Schiff Base complexes stabilize non-fibrillar amyloid-β aggregates with reduced toxicity","abstract":"Abstract The aggregation of Aβ is believed to be foundational to the pathogenesis of Alzheimer’s disease (AD). In vitro aggregation kinetics have been shown to correlate with rates of disease progression in both AD patients and animal models, thus proving to be a useful metric for testing Aβ-targeted therapeutics. Here we present evidence of Cobalt(III) Schiff base complex (Co(III)-sb) modulation of Aβ aggregation kinetics by a variety of complementary techniques. These include Thioflavin T (ThT) fluorescence, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and atomic force microscopy (AFM). Our data was fitted to kinetic rate laws using a mathematical model developed by Knowles et al. in order to extract mechanistic information about the effect of Co(III)-sb on aggregation kinetics. Our analysis revealed that Co(III)-sb significantly decreases the kinetic parameter k +, and significantly increases the polymerization rate k n , suggesting that Co(III)-sb causes Aβ to rapidly form stable oligomeric species that are unable to elongate into mature fibrils. This result was corroborated by TEM and AFM of Aβ aggregates in vitro . We also demonstrate that Aβ aggregate mixtures produced in the presence of Co(III)-sb exhibit decreased cytotoxicity compared to untreated samples. Statement of Significance Amyloid-β is thought to be a key mediator in the pathology of Alzheimer’s disease, yet its precise mechanisms of toxicity are poorly understood. The interaction of Aβ with endogenous metal ions via its N terminal Histidine residues has been shown to alter the peptide’s aggregation and toxicity. As such, metal-based complexes have been developed both as therapeutic agents as well as tools for investigating the role of metal binding in the pathogenesis of AD. This work expands on our previous studies developing Cobalt(III) Schiff base complexes as amyloid inhibitors. Here we demonstrate effective inhibition of aggregation by various complementary modalities. Additionally we show that Co(III)-sb reduces the toxicity of Aβ aggregates to cells in culture.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":129660,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":427919,"name":"Christopher R. Brue","orcid":"0000-0001-9428-9922","position":1,"is_corresponding":false},{"id":581305,"name":"Alex Preston","orcid":"0000-0003-0334-0679","position":2,"is_corresponding":false},{"id":581306,"name":"David Baxter","orcid":"0000-0003-2968-6950","position":3,"is_corresponding":false},{"id":581937,"name":"E. Herzog","orcid":null,"position":4,"is_corresponding":false},{"id":427920,"name":"Eleni A. Varelas","orcid":"0000-0002-4814-4279","position":5,"is_corresponding":false},{"id":381519,"name":"Thomas J. Meade","orcid":"0000-0001-6202-1155","position":6,"is_corresponding":false},{"id":427918,"name":"Kaleigh F. Roberts","orcid":"0000-0001-6483-9153","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:15:49.682497Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}