Grazing-Incidence Neutron-Induced Fluorescence Probes Density Profiles of Labeled Molecules at Solid/Liquid Interfaces

We report on the use of characteristic prompt γ-fluorescence after neutron capture induced by an evanescent neutron wave to probe densities and depth profiles of labeled molecules at solid/liquid interfaces. In contrast to classical scattering techniques and X-ray fluorescence, this method of “grazing-incidence neutron-induced fluorescence” combines direct chemical specificity, provided by the label, with sensitivity to the interface, inherent to the evanescent wave. We demonstrate that the formation of a supported lipid membrane can be quantitatively monitored from the characteristic fluorescence of ¹⁵⁷Gd³⁺ ions bound to the headgroup of chelator lipids. Moreover, we were able to localize the ¹⁵⁷Gd³⁺ ions along the surface normal with nanometer precision. This first proof of principle with a well-defined model system suggests that the method has a great potential for biology and soft matter studies where spatial resolution and chemical sensitivity are required

Development of a Potent Nurr1 Agonist Tool for In Vivo Applications

Nuclear receptor related 1 (Nurr1) is a neuroprotective transcription factor and an emerging target in neurodegenerative diseases. Despite strong evidence for a role in Parkinson’s and Alzheimer’s disease, pharmacological control and validation of Nurr1 are hindered by a lack of suitable ligands. We have discovered considerable Nurr1 activation by the clinically studied dihydroorotate dehydrogenase (DHODH) inhibitor vidofludimus calcium and systematically optimized this scaffold to a Nurr1 agonist with nanomolar potency, strong activation efficacy, and pronounced preference over the highly related receptors Nur77 and NOR1. The optimized compound induced Nurr1-regulated gene expression in astrocytes and exhibited favorable pharmacokinetics in rats, thus emerging as a superior chemical tool to study Nurr1 activation in vitro and in vivo

Development of a Potent Nurr1 Agonist Tool for In Vivo Applications

Nuclear receptor related 1 (Nurr1) is a neuroprotective transcription factor and an emerging target in neurodegenerative diseases. Despite strong evidence for a role in Parkinson’s and Alzheimer’s disease, pharmacological control and validation of Nurr1 are hindered by a lack of suitable ligands. We have discovered considerable Nurr1 activation by the clinically studied dihydroorotate dehydrogenase (DHODH) inhibitor vidofludimus calcium and systematically optimized this scaffold to a Nurr1 agonist with nanomolar potency, strong activation efficacy, and pronounced preference over the highly related receptors Nur77 and NOR1. The optimized compound induced Nurr1-regulated gene expression in astrocytes and exhibited favorable pharmacokinetics in rats, thus emerging as a superior chemical tool to study Nurr1 activation in vitro and in vivo