Metallotexaphyrins as MRI-Active Catalytic Antioxidants for Neurodegenerative Disease: A Study on Alzheimer’s Disease

Brewster II, James T.; Thiabaud, Gregory D.; Harvey, Peter; Zafar, Hadiqa; Reuther, James F.; Dell'Acqua, Simone; Johnson, Rachel M.; Root, Harrison D.; Metola, Pedro; Jasanoff, Alan; Casella, Luigi; Sessler, Jonathan L.

Abstract

The complex etiology of neurodegeneration continues to stifle efforts to develop effective therapeutics. New agents elucidating key pathways causing neurodegeneration might serve to increase our understanding and potentially lead to improved treatments. Here, we demonstrate that a water soluble manganese(II) texaphyrin (MMn) is a suitable magnetic resonance imaging (MRI) contrast agent for detecting larger amyloid beta constructs. The imaging potential of MMn was inferred on the basis of in vitro studies and in vivo detection in Alzheimer's disease C. elegans models using MRI and ICP-MS. In vitro antioxidant and cellular-based assays provide support for the notion that this porphyrin analogue shows promise as a therapeutic agent able to mitigate the oxidative and nitrative toxic effects considered causal in neurodegeneration. The present report marks the first elaboration of an MRI-active metalloantioxidant that confers diagnostic and therapeutic benefit in Alzheimer's disease models without conjugation of a radioisotope, targeting moiety, or therapeutic payload.

Citation

Brewster II, J. T., Thiabaud, G. D., Harvey, P., Zafar, H., Reuther, J. F., Dell'Acqua, S., …Sessler, J. L. (2020). Metallotexaphyrins as MRI-Active Catalytic Antioxidants for Neurodegenerative Disease: A Study on Alzheimer’s Disease. Chem, 6(3), 703-724. https://doi.org/10.1016/j.chempr.2019.12.016

• Journal Article Type: Article
• Acceptance Date: Dec 13, 2019
• Online Publication Date: Jan 9, 2020
• Publication Date: Mar 12, 2020
• Deposit Date: Dec 19, 2019
• Publicly Available Date: Dec 19, 2019
• Journal: Chem
• Electronic ISSN: 2451-9294
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 3
• Pages: 703-724
• DOI: https://doi.org/10.1016/j.chempr.2019.12.016
• Keywords: Materials Chemistry; Biochemistry; General Chemistry; General Chemical Engineering; Biochemistry, medical; Environmental Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/3600895
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2451929419305637?via%3Dihub