Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor.

The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an important therapeutic target in diabetes and obesity. Recent studies in experimental animals have shown that certain subsets of T cells express functional GLP-1R, indicating an immune regulatory role of GLP-1. In contrast, less is known about the expression and function of the GLP-1R in human T cells.

Systemic administration of ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel inhibitor, blocks spontaneous absence seizures.

Objective: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to be involved in the generation of absence seizures (ASs), and there is evidence that cortical and thalamic HCN channel dysfunctions may have a proabsence role. Many HCN channel blockers are available, but their role in ASs has been investigated only by localized brain injection or in in vitro model systems due to their limited brain availability. Here, we investigated the effect on ASs of orally administered ivabradine (an HCN channel blocker approved for the treatment of heart failure in humans) following injection of the P-glycoprotein inhibitor elacridar, which is known to increase penetration into the brain of drug substrates for this efflux transporter.

Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations.

Genetic risk for psychiatric illness is complex, so identification of shared molecular pathways where distinct forms of genetic risk might coincide is of substantial interest. A growing body of genetic and genomic studies suggest that such shared molecular pathways exist across disorders with different clinical presentations, such as schizophrenia and autism spectrum disorder (ASD). But how this relates to specific genetic risk factors is unknown.

The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function.

The identification of the novel and selective GPR3 inverse agonist AF64394, the first small molecule inhibitor of GPR3 receptor function, is described. Structure activity relationships and syntheses based around AF64394 are reported.

A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter.

The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence believed to bind synaptic scaffolding proteins, but its functional significance is uncertain.