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Biology subjects

Riemens, R.

Publications and source records attributed to Riemens, R..

2 recordsLinked to original sources

Remote magnetomechanical neuromodulation uncovers a novel therapeutic mechanism for alleviating Parkinsonian symptoms in freely moving mice

To overcome the limitations of invasive neuromodulation systems, we introduce a wireless magnetomechanical approach for remote, minimally invasive deep brain stimulation (DBS) without chronically implanted electrodes. This method leverages biocompatible nanoscale magnetite nanodiscs (MNDs) with ground vortex magnetisation, which undergo in-plane transitions under low-frequency alternating magnetic fields, thereby generating localised piconewton-scale torques. These torques engage endogenous mechanosensory pathways to modulate neural activity, enabling reversible stimulation without the need for genetic modifications. Calcium imaging validated the rapid neuromodulatory effects of MNDs in vitro and ex vivo, which motivated the subsequent application of magnetomechanical DBS to the subthalamic nucleus in mice. We demonstrated the remote control of motor behaviour in wild-type mice and significant restoration of motor function in a severe hemiparkinsonian model. This study established the first wireless therapeutic magnetomechanical neuromodulation platform that leverages biocompatible nanomaterials and endogenous mechanosensory ion channels, representing a promising step toward untethered, clinically translatable neurotechnology.

neuroscience↗

Inhibition of constitutive activity of the atypical chemokine receptor ACKR3 by the small-molecule inverse agonist VUF16840

The atypical chemokine receptor 3 (ACKR3) has emerged as a promising drug target for the treatment of cancer, cardiovascular, and autoimmune diseases. In this study, we present the pharmacological characterization of VUF16840, the first small-molecule inverse agonist of ACKR3. VUF16840 effectively displaces CXCL12 binding to ACKR3 and inhibits chemokine-induced {beta}-arrestin2 recruitment in a concentration-dependent manner. Furthermore, VUF16840 stabilizes the inactive conformation of ACKR3, as demonstrated by its ability to suppress constitutive {beta}-arrestin2 recruitment. This inverse agonism alters ACKR3 constitutive trafficking, leading to receptor enrichment at the plasma membrane and inhibition of intracellular CXCL12 uptake. Importantly, VUF16840 exhibits high selectivity for ACKR3 over a broad panel of human chemokine receptors. These findings establish VUF16840 as a potent and selective ACKR3 inverse agonist capable of modulating constitutive and chemokine-induced signaling and internalization events. As such, VUF16840 represents a valuable pharmacological tool for exploring the molecular and translational roles of ACKR3 in both physiological and pathological contexts.

pharmacology and toxicology↗