Once neurons are adorned with DREADDs, or designer receptors exclusively activated by designer drugs, neural circuits can be activated or suppressed at will, potentially resolving neurological conditions.

In the past decade, emerging synthetic biology technologies such as chemogenetics have dramatically transformed how pharmacologists and systems biologists deconstruct the involvement of G protein–coupled receptors (GPCRs) in a myriad of physiological and translational settings. Here we highlight a specific chemogenetic application that extends the utility of the concept of RASSLs (receptors activated solely by synthetic ligands): We have dubbed it DREADDs (designer receptors exclusively activated by designer drugs). As we show in this review, DREADDs are now used ubiquitously to modulate GPCR activity noninvasively in vivo. Results from these studies have directly implicated GPCR signaling in a large number of therapeutically relevant contexts. We also highlight recent applications of DREADD technology that have illuminated GPCR signaling processes that control pathways relevant to the treatment of eating disorders, obesity, and obesity-associated metabolic abnormalities. Additionally, we provide an overview of the potential utility of chemogenetic technologies for transformative therapeutics.

Molecular Physiology and Pathology of the Retina Stephen H. Tsang Peter Gouras We have made great progress over the past decade in understanding both the mechanism of phototransduction and the neur…

Chemogenetic tools such as designer receptors exclusively activated by designer drugs (DREADDs) are routinely used to modulate neuronal and non-neuronal signaling and activity in a relatively noninvasive manner. The first generation of DREADDs were templated from the human muscarinic acetylcholine receptor family and are relatively insensitive to the endogenous agonist acetylcholine but instead are activated by clozapine-N-oxide (CNO). Despite the undisputed success of CNO as an activator of muscarinic DREADDs, it has been known for some time that CNO is subject to a low rate of metabolic conversion to clozapine, raising the need for alternative chemical actuators of muscarinic-based DREADDs. Here we show that DREADD agonist 21 (C21) (11-(1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine) is a potent and selective agonist at both excitatory (hM3Dq) and inhibitory (hM4Di) DREADDs and has excellent bioavailability, pharmacokinetic properties, and brain penetrability. We also show that C21-induced activation of hM3Dq and hM4Di in vivo can modulate bidirectional feeding in defined circuits in mice. These results indicate that C21 represents an alternative to CNO for in vivo studies where metabolic conversion of CNO to clozapine is a concern.

Hello Bio manufacture higih quality DREADD receptor ligands Clz N Oxide (CNO), Salvinorin B (SalB), J60, J52 and perlapine which activate DREADD receptors in neuroscience research

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Abstract. Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer dr

A new tool called Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allows us to hijack cell signaling to study cell function.

Pablo Eisenberg, Thomas R. Asher and Jim Abernathy founded NCRP with initial funding provided by John D. Rockefeller III, John Filer and Rockefeller Brothers Fund. Historically, philanthropy as a sector was largely unregulated and unaccountable. After the Tax Reform Act of 1969, Congress began to closely examine foundations, which exerted tremendous social influence. In 1973, […]

During the past few years, CNO-sensitive designer G protein-coupled receptors (GPCRs) known as DREADDs ( designer receptors exclusively activated by designer drugs) have emerged as powerful new tools...

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Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are genetically modified G-protein-coupled receptors (GPCRs), that can be activated by...

Spinal cord injury (SCI) often damages, not only white matter axon tracts that transmits signals to and from the brain, but also the central gray matter, causin...

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