Receptor activated solely by a synthetic ligand

"DREADD" redirects here. Not to be confused with dread or dredd.

A receptor activated solely by a synthetic ligand (RASSL) or designer receptor exclusively activated by designer drugs (DREADD), is a class of artificially engineered protein receptors used in the field of chemogenetics which are selectively activated by certain ligands.[1] They are used in biomedical research, in particular in neuroscience to manipulate the activity of neurons.[2]

Originally differentiated by the approach used to engineer them, RASSLs and DREADDs are often used interchangeably now to represent an engineered receptor-ligand system.[3] These systems typically utilize G protein-coupled receptors (GPCR) engineered to respond exclusively to synthetic ligands, like clozapine N-oxide (CNO),[4] and not to endogenous ligands. Several types of these receptors exists, derived from muscarinic or κ-opioid receptors.[1]

  1. ^ a b Roth BL (February 2016). "DREADDs for Neuroscientists". Neuron. 89 (4): 683–94. doi:10.1016/j.neuron.2016.01.040. PMC 4759656. PMID 26889809.
  2. ^ Campbell, Erin J.; Marchant, Nathan J. (April 2018). "The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats". British Journal of Pharmacology. 175 (7): 994–1003. doi:10.1111/bph.14146. ISSN 1476-5381. PMC 5843707. PMID 29338070.
  3. ^ Conklin BR, Hsiao EC, Claeysen S, Dumuis A, Srinivasan S, Forsayeth JR, Guettier JM, Chang WC, Pei Y, McCarthy KD, Nissenson RA, Wess J, Bockaert J, Roth BL (August 2008). "Engineering GPCR signaling pathways with RASSLs". Nature Methods. 5 (8): 673–8. doi:10.1038/nmeth.1232. PMC 2703467. PMID 18668035.
  4. ^ Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL (March 2007). "Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand". Proceedings of the National Academy of Sciences of the United States of America. 104 (12): 5163–8. Bibcode:2007PNAS..104.5163A. doi:10.1073/pnas.0700293104. PMC 1829280. PMID 17360345.