Background & aim: Psychiatric compounds modulate complex brain networks, making whole-brain assessment of neuronal activity essential for understanding their mechanisms of action. Activity-dependent genes such as c-Fos, and other stimulus-regulated genes (SRGs) provide complementary molecular readouts of neuronal activation, and…
Background & aim: Central regulation of appetite and satiety engages neuronal populations distributed across the brain. The identification of novel drug targets, development of anti-obesity therapeutics, and validation of their mode of action benefit from whole-brain imaging. Light-sheet fluorescence…
Background & aim: Neurodegenerative diseases are characterized by complex, large-scale structural and cellular alterations across the brain. Understanding these changes requires comprehensive, whole-brain analysis at high spatial resolution. Three-dimensional light sheet fluorescence microscopy (3D LSFM) enables rapid imaging of intact…
Abstract: Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here,…
Background: Injectable peptide-based glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are effective treatments for obesity and diabetes but are limited by patient compliance and scalability challenges. In contrast, non-peptide small-molecule GLP1RAs offer the advantage of oral delivery but are relatively inactive…
Background & aim: Nutrient-stimulated gut hormone peptide YY3e36 (PYY3e36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy…
Background & aim: Injectable peptide-based GLP-1 receptor agonists (GLP1RAs) are effective treatments for obesity and type 2 diabetes, yet present challenges related to patient compliance and scalable production. In contrast, small-molecule GLP1RAs offer significant advantages, including oral bioavailability and scalable…
