Brewster 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
Department of Chemistry, the University of Texas at Austin, Austin, TX 78712-1224, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Chem. 2020 Mar 12;6(3):703-724. doi: 10.1016/j.chempr.2019.12.016.
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 studies and detection in Alzheimer's disease models via MRI and ICP-MS. antioxidant- and cellular-based assays provide support for the notion that this porphyrin analog 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.
神经退行性变的复杂病因持续阻碍着开发有效治疗方法的努力。阐明导致神经退行性变的关键途径的新药物可能有助于增进我们的理解，并有可能带来更好的治疗方法。在此，我们证明水溶性锰（II） texaphyrin（MMn）是一种适用于检测较大淀粉样β聚集体的磁共振成像（MRI）造影剂。MMn的成像潜力是基于相关研究以及通过MRI和电感耦合等离子体质谱（ICP-MS）在阿尔茨海默病模型中的检测推断得出的。基于抗氧化剂和细胞的检测为以下观点提供了支持：这种卟啉类似物有望成为一种治疗剂，能够减轻被认为是神经退行性变病因的氧化和硝化毒性作用。本报告首次阐述了一种具有MRI活性的金属抗氧化剂，它在阿尔茨海默病模型中无需结合放射性同位素、靶向部分或治疗载荷即可带来诊断和治疗益处。
