Alpha 2.0
Login Register
» Articles » PMID: 31072638

Designer Drugs for Designer Receptors: Unlocking the Translational Potential of Chemogenetics

Overview
Journal Trends Pharmacol Sci
Specialty Pharmacology
Date 2019 May 11
PMID 31072638
Citations 2
Authors
Ofer Yizhar
J Simon Wiegert
Affiliations
Soon will be listed here.
Abstract

Chemogenetic techniques allow selective manipulation of neurons by activating engineered actuator proteins with otherwise inert effector molecules. A recent study (Magnus et al. Science 2019;364:eaav5282) describes the coevolution of highly potent actuator-effector pairs based on a clinically approved antismoking drug. These tools allow selective excitation or inhibition of neurons in the living brain with high specificity and no detectable side-effects.

Citing Articles

Chemogenetics with PSAM-GlyR decreases excitability and epileptiform activity in epileptic hippocampus.

Gonzalez-Ramos A, Berglind F, Kudlacek J, Rocha E, Melin E, Sebastiao A Gene Ther. 2024; .

PMID: 39455855 DOI: 10.1038/s41434-024-00493-7.

PET reporter systems for the brain.

Nerella S, Michaelides M, Minamimoto T, Innis R, Pike V, Eldridge M Trends Neurosci. 2023; 46(11):941-952.

PMID: 37734962 PMC: 10592100. DOI: 10.1016/j.tins.2023.08.007.

References
1.
Armbruster B, Li X, Pausch M, Herlitze S, Roth B . Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci U S A. 2007; 104(12):5163-8. PMC: 1829280. DOI: 10.1073/pnas.0700293104. View
2.
Magnus C, Lee P, Atasoy D, Su H, Looger L, Sternson S . Chemical and genetic engineering of selective ion channel-ligand interactions. Science. 2011; 333(6047):1292-6. PMC: 3210548. DOI: 10.1126/science.1206606. View
3.
Sternson S, Roth B . Chemogenetic tools to interrogate brain functions. Annu Rev Neurosci. 2014; 37:387-407. DOI: 10.1146/annurev-neuro-071013-014048. View
4.
Chen X, Choo H, Huang X, Yang X, Stone O, Roth B . The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs. ACS Chem Neurosci. 2015; 6(3):476-84. PMC: 4368042. DOI: 10.1021/cn500325v. View
5.
Doyon N, Vinay L, Prescott S, De Koninck Y . Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition. Neuron. 2016; 89(6):1157-1172. DOI: 10.1016/j.neuron.2016.02.030. View