Looking for Novelty in an “Old” Receptor: Recent Advances Toward Our Understanding of GABAARs and Their Implications in Receptor Pharmacology
Year: 2021
Type: review
Abstract: Diverse populations of GABAA receptors (GABAARs) throughout the brain mediate fast inhibitory transmission and are modulated by various endogenous ligands and therapeutic drugs. Deficits in GABAAR signaling underlie the pathophysiology behind neurological and neuropsychiatric disorders such as epilepsy, anxiety, and depression. Pharmacological intervention for these disorders relies on several drug classes that target GABAARs, such as benzodiazepines and more recently neurosteroids. It has been widely demonstrated that subunit composition and receptor stoichiometry impact the biophysical and pharmacological properties of GABAARs. However, current GABAAR-targeting drugs have limited subunit selectivity and produce their therapeutic effects concomitantly with undesired side effects. Therefore, there is still a need to develop more selective GABAAR pharmaceuticals, as well as evaluate the potential for developing next-generation drugs that can target accessory proteins associated with native GABAARs. In this review, we briefly discuss the effects of benzodiazepines and neurosteroids on GABAARs, their use as therapeutics, and some of the pitfalls associated with their adverse side effects. We also discuss recent advances toward understanding the structure, function, and pharmacology of GABAARs with a focus on benzodiazepines and neurosteroids, as well as newly identified transmembrane proteins that modulate GABAARs.
Source: Frontiers in Neuroscience
Authors: David Castellano, Ryan David Shepard, Wei Lu
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W3118727329