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Chemogenetic approaches to identify metabolically important GPCR signaling pathways: Therapeutic implications
Author(s) -
Meister Jaroslawna,
Wang Lei,
Pydi Sai P.,
Wess Jürgen
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15314
Subject(s) - heterotrimeric g protein , g protein coupled receptor , receptor , neuroscience , signal transduction , biology , g protein , muscarinic acetylcholine receptor , drug discovery , functional selectivity , microbiology and biotechnology , bioinformatics , biochemistry
Abstract DREADDs (Designer Receptors Exclusively Activated by a Designer Drug) are designer G protein‐coupled receptors (GPCRs) that are widely used in the neuroscience field to modulate neuronal activity. In this review, we will focus on DREADD studies carried out with genetically engineered mice aimed at elucidating signaling pathways important for maintaining proper glucose and energy homeostasis. The availability of muscarinic receptor‐based DREADDs endowed with selectivity for one of the four major classes of heterotrimeric G proteins (G s , G i , G q , and G 12 ) has been instrumental in dissecting the physiological and pathophysiological roles of distinct G protein signaling pathways in metabolically important cell types. The novel insights gained from this work should inform the development of novel classes of drugs useful for the treatment of several metabolic disorders including type 2 diabetes and obesity.