Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression.

Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology.

Heterobivalent Dual-Target Peptide for Integrin-αβ and Neuropeptide Y Receptors on Breast Tumor.

Heterodimer peptides targeting more than one receptor can be advantageous, as tumors can simultaneously express more than one receptor type. For human breast cancer, a promising biological target is tumor angiogenesis through αβ integrin expression. Another promising target is Neuropeptide Y receptors, considering YR is overexpressed in 90% of human breast tumors.

Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An in vivo microPET study.

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non-invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS.