Molecular Characterization of GABA-A Receptor Subunit Diversity within Major Peripheral Organs and Their Plasticity in Response to Early Life Psychosocial Stress

Frontiers in Molecular Neuroscience
Ethan A EveringtonMohsen Seifi

Abstract

Gamma aminobutyric acid (GABA) subtype A receptors (GABAARs) are integral membrane ion channels composed of five individual proteins or subunits. Up to 19 different GABAAR subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3) have been identified, resulting in anatomically, physiologically, and pharmacologically distinct multiple receptor subtypes, and therefore GABA-mediated inhibition, across the central nervous system (CNS). Additionally, GABAAR-modulating drugs are important tools in clinical medicine, although their use is limited by adverse effects. While significant advances have been made in terms of characterizing the GABAAR system within the brain, relatively less is known about the molecular phenotypes within the peripheral nervous system of major organ systems. This represents a potentially missed therapeutic opportunity in terms of utilizing or repurposing clinically available GABAAR drugs, as well as promising research compounds discarded due to their poor CNS penetrance, for the treatment of peripheral disorders. In addition, a broader understanding of the peripheral GABAAR subtype repertoires will contribute to the design of therapies which minimize peripheral side-effects when treating CNS disorders. We have recent...Continue Reading

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Citations

Sep 9, 2020·Assay and Drug Development Technologies·Hermann A M Mucke
Jul 10, 2019·Pharmacology & Therapeutics·Marie-Christine TononJérôme Leprince
Jun 8, 2021·Frontiers in Psychiatry·Tori L SchaeferCraig A Erickson
Oct 16, 2021·Experimental Biology and Medicine·Debanjan BhattacharyaSoma Sengupta

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