Wallstein Niklas, Capucciati Andrea, Pöppl Andreas, Schnohr Claudia S, Sturini Michela, Pampel André, Jäger Carsten, Zecca Luigi, Zucca Fabio A, Monzani Enrico, Casella Luigi, Möller Harald E
NMR Methods & Development Group, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1A, 04103, Leipzig, Germany.
Department of Chemistry, University of Pavia, Via Taramelli 12, Pavia, 27100, Italy.
Angew Chem Int Ed Engl. 2025 Oct 6;64(41):e202509102. doi: 10.1002/anie.202509102. Epub 2025 Sep 19.
Neuromelanin (NM) is a dark pigment that binds potentially toxic metal ions and is crucial for neuronal vulnerability. Magnetic resonance imaging (MRI) was proposed to measure neuromelanin in the substantia nigra or locus coeruleus, potentially providing a marker of Parkinson's disease. Here, synthetic neuromelanin analogues were prepared with iron and copper and used for characterization of metal binding and impact on proton relaxation, a prerequisite for optimizing neuromelanin-sensitive MRI. The results confirm the presence of paramagnetic mononuclear Fe(III) and antiferromagnetically coupled clusters, which enhance relaxation to variable degrees. Further complexity arises from Cu(II), which can compete for binding to mononuclear sites, aggregate in mixed-metal clusters, or bind to proteins associated with the melanin moiety. Unlike the strong relaxant Fe(III), Cu(II) only indirectly impacts relaxation by replacing iron. Overall, MRI primarily provides measures of average neuromelanin concentrations. Information on the distribution of neuromelanins with different metal compositions might be obtained with multiparametric MRI.
神经黑色素（NM）是一种深色色素，它能结合潜在有毒金属离子，对神经元易损性至关重要。有人提出利用磁共振成像（MRI）测量黑质或蓝斑中的神经黑色素，这可能为帕金森病提供一个标志物。在此，用铁和铜制备了合成神经黑色素类似物，并用于表征金属结合情况以及对质子弛豫的影响，这是优化神经黑色素敏感MRI的一个前提条件。结果证实存在顺磁性单核Fe(III)和反铁磁耦合簇，它们会不同程度地增强弛豫。Cu(II)会带来进一步的复杂性，它可以竞争单核位点的结合、在混合金属簇中聚集或与与黑色素部分相关的蛋白质结合。与强弛豫剂Fe(III)不同，Cu(II)仅通过取代铁间接影响弛豫。总体而言，MRI主要提供平均神经黑色素浓度的测量值。利用多参数MRI可能获得关于不同金属组成的神经黑色素分布的信息。
